{"gene":"FUBP1","run_date":"2026-06-09T23:54:44","timeline":{"discoveries":[{"year":2023,"finding":"FUBP1 is a general splicing factor that binds a novel cis-regulatory motif and stabilizes U2AF2 and SF1 (key 3' splice site components) through multivalent binding interfaces in its disordered regions; it is required for efficient splicing of long introns (representing ~80% of human introns) and interacts with U1 snRNP-associated proteins, suggesting a role in splice site bridging. NMR, structural, and in vivo interaction data, plus transcriptional profiling and kinetic modeling, support this model.","method":"NMR, crystal structures, in vivo CLIP/interaction data, transcriptional profiling, kinetic modeling, mutagenesis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal methods (NMR, structural data, in vivo interaction, transcriptional profiling, kinetic modeling) in a single rigorous study","pmids":["37506698"],"is_preprint":false},{"year":2020,"finding":"Crystal structures of all four KH domains (KH1–4) of FUBP1 show they are highly conserved topologically and each can independently bind the FUSE ssDNA sequence; KH3 shows higher nucleotide-binding potency; differences in amino acid composition at the binding cleft account for diverse nucleotide-sequence preferences among KH1–4; cooperativity of all four KH modules is required for nanomolar-affinity FUSE binding.","method":"X-ray crystallography, ssDNA-binding characterization (biophysical assays)","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structures of all four KH domains plus binding characterization in a single rigorous paper","pmids":["32778776"],"is_preprint":false},{"year":2014,"finding":"FUBP1 binds discrete cis-regulatory elements within intron 11 of MDM2 pre-mRNA and acts as a positive splicing regulator; blocking FUBP1 function in in vitro splicing reactions decreased splicing efficiency, and FUBP1 knockdown in cells induced formation of the stress-induced MDM2-ALT1 splice variant under normal conditions.","method":"In vitro splicing assays, RNA binding assays, siRNA knockdown, minigene splicing reporter","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro splicing reconstitution plus cell-based knockdown with defined molecular phenotype in a single study","pmids":["24798327"],"is_preprint":false},{"year":2015,"finding":"FUBP1 promotes constitutive inclusion of DMD exon 39 by binding a functional intronic splicing enhancer (ISE) in intron 38; binding was established by RNA pulldown, RNA EMSA, and RNA-ChIP on endogenous DMD pre-mRNA; serial deletion and mutagenesis of minigenes delineated the functional ISE.","method":"RNA pulldown, RNA EMSA, RNA-ChIP, minigene deletion/mutagenesis analysis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal in vitro and in-cell methods including mutagenesis and ChIP on endogenous pre-mRNA","pmids":["25662218"],"is_preprint":false},{"year":2019,"finding":"FUBP1 participates in regulating N6-methyladenosine (m6A) RNA methylation; its loss leads to global changes in RNA splicing and widespread expression of aberrant driver isoforms, as demonstrated by an in vivo CRISPR screen identifying FUBP1 as a long-tail tumor suppressor that cooperates with other tumor suppressor genes to transform mammary epithelial cells.","method":"In vivo CRISPR screen, RNA splicing profiling, m6A methylation analysis","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo CRISPR screen plus splicing/m6A profiling, single lab, two orthogonal approaches","pmids":["31553912"],"is_preprint":false},{"year":2025,"finding":"FUBP1 is an Nm (2'-O-methylation) RNA-binding protein: EMSA validated preference of FUBP1 for Nm-modified RNA; FUBP1 predominantly binds intronic regions; Nm sites in chromatin-associated RNA (caRNA) overlap with FUBP1-binding sites; Nm depletion reduced FUBP1 occupancy on modified regions; FUBP1 depletion induced exon skipping in Nm-modified genes, establishing FUBP1 as a mediator of Nm-dependent splicing regulation.","method":"RNA affinity purification/mass spectrometry, EMSA, caRNA Nm profiling, ChIP-seq/CLIP, siRNA depletion with splicing analysis","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal biochemical and genomic methods (EMSA, affinity purification/MS, occupancy profiling, splicing analysis upon depletion) in a single study","pmids":["41105785"],"is_preprint":false},{"year":2015,"finding":"FUBP1 is essential for fetal and adult hematopoietic stem cell (HSC) self-renewal; conditional functional inactivation in two mouse models caused embryonic lethal anemia (~E15.5) with severely diminished HSCs; FUBP1-deficient HSCs showed intrinsic defects in maintenance and long-term reconstitution, with upregulation of cell-cycle inhibitor p21 and pro-apoptotic Noxa, leading to increased generation time and HSC death tracked by video-microscopy.","method":"Conditional knockout mouse models (two independent models), transplantation assays, video-microscopy cell tracking, transcriptional analysis","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — two independent mouse KO models, multiple cellular and molecular readouts, replicated phenotype","pmids":["26095368"],"is_preprint":false},{"year":2018,"finding":"RUNX1 and FUBP1 interact in the same transcriptional regulatory complex in human B-cell precursor lymphoblasts and co-occupy active chromatin at the c-KIT locus, including a novel FUBP1 FUSE-like binding sequence at +30 kb enhancer; FUBP1 and RUNX1 cooperate to upregulate c-KIT expression, promoting cell proliferation and resistance to imatinib.","method":"Co-immunoprecipitation, ChIP-seq, enhancer characterization, luciferase reporter, functional proliferation assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, ChIP-seq, functional reporter and proliferation assays, multiple orthogonal methods in single study","pmids":["30500954"],"is_preprint":false},{"year":2018,"finding":"FUBP1 is a novel binding partner of adenovirus 5 E1A; FUBP1 binds directly to E1A via its N-terminus (residues 1–82) and conserved region 3 (residues 139–204); FUBP1 depletion reduces virus growth and activates p53-regulated genes; during infection FUBP1 is relocalized within the nucleus, recruited to viral promoters with E1A while lost from the FUSE upstream of c-Myc; FUBP1 suppresses p53 DNA binding, and E1A stabilizes the FUBP1-p53 complex to prevent p53 promoter binding.","method":"Co-immunoprecipitation, siRNA depletion, ChIP, gene expression analysis, domain mapping","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding mapped to domains, ChIP relocalization data, functional p53 and viral growth readouts in a single study","pmids":["29743362"],"is_preprint":false},{"year":2017,"finding":"Camptothecin (CPT) and its derivative SN-38 (active irinotecan metabolite) inhibit FUBP1 activity by preventing FUBP1 binding to its single-stranded DNA target FUSE in vitro, and induce deregulation of FUBP1 target genes in HCC cells.","method":"In vitro DNA binding assay (FUBP1/FUSE interaction), gene expression analysis in HCC cells, drug library screen","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro biochemical assay demonstrating inhibition of FUBP1-FUSE interaction, plus cell-based gene expression, single lab","pmids":["29031818"],"is_preprint":false},{"year":2016,"finding":"Pyrazolo[1,5a]pyrimidine-based compounds (e.g., compound 6) inhibit FUBP1 binding to its single-stranded DNA target FUSE with IC50 of 11.0 μM in biophysical assays, and reduce expansion and induce death in hepatocellular carcinoma cells.","method":"Biophysical binding assay (FUBP1-FUSE interaction), cell viability assay, medium-throughput screening","journal":"Bioorganic & medicinal chemistry","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — biochemical FUSE binding assay with IC50, cell-based validation, single lab and single study","pmids":["27729195"],"is_preprint":false},{"year":2021,"finding":"FUBP1 binds the Nrf2 5'UTR in response to H2O2 (identified by LC-MS/MS, Far Western blot, and RNP-IP); FUBP1 undergoes cytosolic redistribution to ribosomal fractions under oxidative stress; FUBP1 gains physical interaction with eIF3η (but not eIF4E, eIF2α, or eIF1) upon H2O2 treatment; FUBP1 promotes 40S ribosomal subunit attachment to Nrf2 mRNA and 43S pre-initiation complex formation, facilitating de novo Nrf2 protein translation under oxidative stress.","method":"LC-MS/MS, Far Western blot, RNP-immunoprecipitation, ribosome fractionation, siRNA knockdown, co-immunoprecipitation with translation initiation factors","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biochemical methods (LC-MS/MS, Far Western, RNP-IP, fractionation, Co-IP), single lab","pmids":["33676361"],"is_preprint":false},{"year":2021,"finding":"FUBP1 promotes colorectal cancer stemness and metastasis by directly binding to the DVL1 promoter to activate DVL1 transcription, thereby activating Wnt/β-catenin signaling and increasing pluripotent transcription factors (c-Myc, NANOG, SOX2); FUBP1 protein stability is regulated by Smurf2-mediated ubiquitin degradation (reduced in KRAS-wild-type CRC) and by caspase-3-dependent cleavage (reduced in KRAS-mutant CRC).","method":"ChIP, luciferase reporter, co-immunoprecipitation, overexpression/knockdown, in vitro and in vivo tumor assays","journal":"Molecular oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and luciferase for direct promoter binding, Co-IP for protein interactions, in vivo validation, single lab","pmids":["34288405"],"is_preprint":false},{"year":2019,"finding":"FUBP1 inhibits HIF1α degradation by downregulating VHL (the E3 ligase for HIF1α), resulting in upregulation of LDHB and enhanced glycolysis in neuroblastoma cells; this pro-glycolytic mechanism is independent of N-Myc regulation.","method":"Luciferase assay, Western blot, ChIP, ELISA for glycolytic metabolites, siRNA knockdown","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — ChIP and luciferase for target gene regulation, multiple metabolic readouts, single lab","pmids":["31511046"],"is_preprint":false},{"year":2019,"finding":"Fubp1 upregulates mRNA levels of hexokinase genes Hk1 and Hk2, supporting aerobic glycolysis and the lactate-Akt-mTOR survival axis in cells; Fubp1 deficiency reduces Hk1/Hk2 expression.","method":"qRT-PCR, Western blot, cell survival assays, metabolic assays","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, expression-level analysis with limited mechanistic depth, no direct binding/ChIP shown","pmids":["30871777"],"is_preprint":false},{"year":2020,"finding":"FUBP1 protein level is enriched in S phase; FUBP1 deficiency alters cell cycle progression in S phase by downregulating Ccna (cyclin A) mRNA expression; FUBP1 deficiency also confers survival advantages against metabolic stress and anti-cancer drugs.","method":"Cell cycle synchronization, flow cytometry, qRT-PCR, Western blot, CRISPR/Cas9 KO cells","journal":"Cells","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, correlation between Fubp1 and cyclin A without direct binding demonstrated, limited mechanistic depth","pmids":["32481602"],"is_preprint":false},{"year":2019,"finding":"CRISPR/Cas9-mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein; Fubp1 upregulates Syncrip (main post-transcriptional regulator of Per1 protein oscillation) at mRNA and protein levels, establishing a Fubp1-Syncrip-Per1 regulatory axis for circadian clock maintenance.","method":"CRISPR/Cas9 knockout, qRT-PCR, Western blot, circadian oscillation profiling","journal":"Cell biology international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect mechanism (Fubp1→Syncrip→Per1) without direct binding or promoter studies shown","pmids":["31535751"],"is_preprint":false},{"year":2019,"finding":"TAL1 directly activates the FUBP1 promoter in erythroid progenitor cells, requiring an intact GATA sequence in a combined E-box/GATA motif; this TAL1-driven FUBP1 expression is required for efficient erythroid differentiation, as FUBP1-deficient progenitors show limited erythroid differentiation capacity.","method":"ChIP, promoter reporter assays, FUBP1 knockdown, erythroid differentiation assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ChIP showing TAL1 binding to FUBP1 promoter, mutagenesis of binding motif, functional differentiation assay, single lab","pmids":["30653565"],"is_preprint":false},{"year":2023,"finding":"FUBP1 is required for NR_109 lncRNA-mediated M2-like macrophage polarization; NR_109 competes with JVT-1 (JTV-1) to bind the C-terminus domain of FUBP1, preventing ubiquitin-mediated degradation of FUBP1, thereby stabilizing FUBP1 and enabling c-Myc transcription activation.","method":"Co-immunoprecipitation, RNA immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vivo tumor models","journal":"Journal for immunotherapy of cancer","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP for protein interaction, ubiquitination assay, functional rescue experiments, single lab","pmids":["37217247"],"is_preprint":false},{"year":2021,"finding":"TNPO1 (Transportin-1) mediates nuclear import of FUBP1 through direct interaction; nuclear FUBP1 regulates transcription of the immune checkpoint gene NRP1; knockdown of FUBP1 inhibits cervical cancer cell proliferation and migration.","method":"Co-immunoprecipitation, nuclear/cytoplasmic fractionation, siRNA knockdown, functional assays","journal":"Journal of immunology research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP for TNPO1-FUBP1 interaction, fractionation data, limited mechanistic follow-up for NRP1 regulation, single lab","pmids":["33987449"],"is_preprint":false},{"year":2020,"finding":"NORAD lncRNA binds the central domain of FUBP1 through multiple regions and attenuates FUBP1 nuclear localization, impairing FUBP1 occupancy on pro-apoptotic gene promoters and thereby inducing apoptosis in endometrial cancer cells; the NORAD-4 fragment sufficient for FUBP1 binding recapitulated the anti-tumor effects in vivo.","method":"RNA pulldown, co-immunoprecipitation, subcellular fractionation/localization, ChIP, xenograft model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal methods (RNA pulldown, Co-IP, fractionation, ChIP, in vivo rescue), single lab","pmids":["32555178"],"is_preprint":false},{"year":2024,"finding":"FUBP1 directly activates USP29 gene transcription (demonstrated by ChIP and luciferase assay); USP29 in turn interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis promoting gastric cancer.","method":"ChIP, luciferase reporter, Co-IP, ubiquitination assay, mass spectrometry, qRT-PCR, xenograft model","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and luciferase for FUBP1 transcriptional activation of USP29, Co-IP and ubiquitination assay for USP29-AURKB axis, single lab","pmids":["38233848"],"is_preprint":false},{"year":2011,"finding":"FUBP1 protein binds the EV71 5'-UTR (an IRES element) as shown by RNA affinity pulldown coupled with LC-MS/MS; kaempferol treatment changes the composition of IRES-associated trans-acting factors including FUBP1, affecting IRES function and EV71 replication.","method":"RNA affinity pull-down, LC-MS/MS","journal":"Food chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown/MS experiment identifying FUBP1 as IRES-binding protein; minimal mechanistic follow-up for FUBP1 specifically","pmids":["25212137"],"is_preprint":false},{"year":2025,"finding":"FUBP1 promotes SPA lncRNA expression via two distinct mechanisms: (1) enhancing transcription of SPA-embedded polycistronic transcripts by targeting a FUSE-like sequence upstream of the promoter, and (2) facilitating SPA1 splicing and maturation by binding U-rich intronic sequences; both FUBP1 and MYEF2 are enriched in Prader-Willi syndrome (PWS) bodies.","method":"ChIP, RNA immunoprecipitation, minigene splicing assays, knockdown with expression analysis, FUSE-like sequence identification","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for transcriptional role, RNA binding and splicing assays, functional knockdown, single lab","pmids":["40147944"],"is_preprint":false},{"year":2020,"finding":"FUBPs enforce epigenetic setpoints that restrict MYC expression; FUBP1/FUBP2-lacking murine embryonic fibroblasts express MYC at levels otherwise attained only after stimulation and show MYC chromatin changes (altered histone marks), establishing that FUBPs constrain MYC expression through chromatin-level regulation in single primary cells.","method":"Single-cell MYC expression tracking, chromatin mark profiling (ChIP for histone modifications), FUBP knockout MEFs and B-cells","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single-cell tracking plus ChIP for chromatin marks, multiple cell types, single lab","pmids":["33005010"],"is_preprint":false},{"year":2025,"finding":"FUBP1 contributes to miR-155-3p expression/maturation from pre-miR-155 in macrophages; FUBP1 may support miR-155-3p for specific subcellular functions, while KSRP inhibits both miR-155-5p and miR-155-3p maturation without altering relative strand expression.","method":"RNA-binding protein knockdown, miRNA quantification, strand-selective miRNA analysis","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, functional knockdown with miRNA measurement but limited mechanistic detail for FUBP1's specific role in processing","pmids":["40825800"],"is_preprint":false}],"current_model":"FUBP1 is a multifunctional single-stranded DNA/RNA-binding protein whose four KH domains cooperatively bind the FUSE element to regulate transcription of target genes (most notably c-MYC and p21); it acts as a general splicing factor that stabilizes U2AF2 and SF1 at 3' splice sites to facilitate splicing of long introns, binds intronic cis-regulatory elements to promote exon inclusion (e.g., MDM2, DMD), participates in m6A and 2'-O-methylation-dependent splicing, mediates de novo Nrf2 translation under oxidative stress via interaction with eIF3η and ribosome recruitment, is required for hematopoietic stem cell self-renewal through transcriptional regulation of p21 and pro-apoptotic genes, cooperates with RUNX1 to activate c-KIT enhancer-driven transcription, is imported into the nucleus by TNPO1, and its FUSE-binding activity can be pharmacologically inhibited by camptothecin/SN-38 and small-molecule FUBP1 inhibitors."},"narrative":{"mechanistic_narrative":"FUBP1 is a multifunctional single-stranded nucleic acid-binding protein that operates as both a transcriptional regulator and a splicing factor, coupling control of gene expression to cell proliferation, hematopoiesis, and cancer [PMID:32778776, PMID:37506698, PMID:26095368]. Its four KH domains are topologically conserved and each independently engages the single-stranded FUSE DNA element, with KH3 showing the highest binding potency and cooperativity among all four modules required for nanomolar-affinity binding [PMID:32778776]. Through this FUSE-binding activity FUBP1 enforces epigenetic setpoints that restrict MYC expression via chromatin-level regulation, and directly activates additional target promoters including DVL1, USP29, and a FUSE-like enhancer at the c-KIT locus where it cooperates with RUNX1 [PMID:33005010, PMID:34288405, PMID:38233848, PMID:30500954]. In parallel, FUBP1 functions as a general splicing factor: it binds a cis-regulatory motif and stabilizes the 3' splice site components U2AF2 and SF1 through multivalent interfaces in its disordered regions, enabling efficient splicing of long introns, and it binds discrete intronic enhancer elements to promote exon inclusion in pre-mRNAs such as MDM2 and DMD [PMID:37506698, PMID:24798327, PMID:25662218]. FUBP1 reads RNA modifications, preferentially binding 2'-O-methylated (Nm) intronic RNA to direct Nm-dependent splicing and participating in m6A-linked splicing regulation [PMID:41105785, PMID:31553912]. Beyond the nucleus, FUBP1 binds the Nrf2 5'UTR under oxidative stress, interacts with eIF3η, and recruits the 40S ribosomal subunit to promote de novo Nrf2 translation [PMID:33676361]. FUBP1 is essential for fetal and adult hematopoietic stem cell self-renewal, its loss causing embryonic lethal anemia and HSC death through upregulation of p21 and the pro-apoptotic gene Noxa [PMID:26095368]. FUBP1 abundance and localization are themselves controlled by ubiquitin-mediated degradation, TNPO1-dependent nuclear import, and antagonistic lncRNAs (NORAD, NR_109) [PMID:37217247, PMID:33987449, PMID:32555178]. Its FUSE-binding activity is pharmacologically inhibited by camptothecin/SN-38 and by pyrazolo[1,5a]pyrimidine compounds [PMID:29031818, PMID:27729195].","teleology":[{"year":2011,"claim":"Identifying FUBP1 among viral IRES-associated factors raised the question of whether FUBP1 engages structured 5'UTR RNA elements beyond its DNA-binding role.","evidence":"RNA affinity pulldown coupled with LC-MS/MS on the EV71 5'-UTR IRES","pmids":["25212137"],"confidence":"Low","gaps":["Single pulldown/MS experiment with no functional follow-up specific to FUBP1","Direct binding versus complex co-purification not distinguished","No mechanism for IRES regulation established"]},{"year":2014,"claim":"Whether FUBP1 acted on pre-mRNA splicing was addressed by showing it binds intronic cis-elements and positively regulates a defined splicing event.","evidence":"In vitro splicing reconstitution, RNA binding, and siRNA knockdown with MDM2 minigene reporters","pmids":["24798327"],"confidence":"High","gaps":["Mechanism of how binding promotes splicing not defined","Generality across other transcripts not established","Spliceosomal contacts not identified"]},{"year":2015,"claim":"FUBP1's role as a sequence-specific intronic splicing enhancer factor was extended by demonstrating it drives constitutive exon inclusion through an endogenous ISE.","evidence":"RNA pulldown, RNA EMSA, RNA-ChIP and minigene mutagenesis on DMD pre-mRNA","pmids":["25662218"],"confidence":"High","gaps":["How ISE binding recruits the splicing machinery unresolved","Whether the same mechanism operates genome-wide unknown"]},{"year":2015,"claim":"The physiological requirement for FUBP1 was established by showing it is intrinsically required for hematopoietic stem cell self-renewal, linking its molecular activity to a developmental phenotype.","evidence":"Two independent conditional knockout mouse models, transplantation, video-microscopy, and transcriptional analysis","pmids":["26095368"],"confidence":"High","gaps":["Whether p21/Noxa regulation is direct transcriptional binding not shown","Splicing versus transcriptional contribution to the phenotype not separated"]},{"year":2017,"claim":"The therapeutic tractability of FUBP1 was probed by identifying clinically used drugs that block its DNA-binding activity.","evidence":"In vitro FUBP1/FUSE binding assay and gene-expression analysis in HCC cells from a drug library screen","pmids":["29031818"],"confidence":"Medium","gaps":["Direct versus indirect inhibition mechanism not resolved","On-target specificity in cells not established","Camptothecin has other primary targets"]},{"year":2016,"claim":"Dedicated small-molecule inhibitors were developed to test whether the FUBP1-FUSE interaction is druggable as an anticancer strategy.","evidence":"Biophysical FUSE-binding assay with IC50 determination and HCC cell viability assays","pmids":["27729195"],"confidence":"Medium","gaps":["Modest potency (IC50 ~11 µM)","Cellular target engagement not confirmed","Selectivity over related KH proteins unknown"]},{"year":2018,"claim":"FUBP1's integration into a defined transcription factor complex was demonstrated by showing it partners with RUNX1 at an enhancer to activate an oncogenic target.","evidence":"Reciprocal Co-IP, ChIP-seq, enhancer characterization, luciferase reporters and proliferation assays in B-cell precursors","pmids":["30500954"],"confidence":"High","gaps":["Direct versus bridged RUNX1-FUBP1 contact not mapped","Whether cooperation extends to other enhancers unknown"]},{"year":2018,"claim":"A viral hijacking mechanism revealed FUBP1's regulation of p53, showing adenovirus E1A binds FUBP1 directly via mapped domains and redirects it to suppress p53.","evidence":"Co-IP with domain mapping, siRNA depletion, ChIP and gene-expression analysis during infection","pmids":["29743362"],"confidence":"Medium","gaps":["Mechanism of FUBP1-mediated p53 DNA-binding suppression not defined","Relevance to uninfected cells unclear"]},{"year":2019,"claim":"FUBP1 was placed in RNA-modification biology by an in vivo screen identifying it as a tumor suppressor whose loss reprograms splicing and m6A.","evidence":"In vivo CRISPR screen with RNA splicing and m6A profiling in mammary epithelial cells","pmids":["31553912"],"confidence":"Medium","gaps":["Direct link between FUBP1 and m6A machinery not established","Mechanism connecting FUBP1 loss to aberrant isoforms unresolved"]},{"year":2019,"claim":"FUBP1's transcriptional output was shown to be itself transcriptionally controlled by TAL1 during erythroid differentiation, embedding it in a lineage-specific regulatory circuit.","evidence":"ChIP, promoter reporter with GATA-motif mutagenesis, knockdown and differentiation assays","pmids":["30653565"],"confidence":"Medium","gaps":["Downstream FUBP1 targets driving differentiation not identified"]},{"year":2019,"claim":"Multiple studies linked FUBP1 to metabolic reprogramming, indicating it supports glycolysis through regulation of VHL/HIF1α and hexokinase gene expression.","evidence":"ChIP, luciferase, metabolite assays in neuroblastoma; qRT-PCR and metabolic assays for Hk1/Hk2","pmids":["31511046","30871777"],"confidence":"Medium","gaps":["Direct promoter binding to Hk1/Hk2 not demonstrated","Mechanism of VHL downregulation not defined"]},{"year":2019,"claim":"An unexpected role in timekeeping was proposed via a FUBP1-Syncrip-Per1 axis controlling circadian oscillation.","evidence":"CRISPR knockout, qRT-PCR, Western blot and circadian profiling","pmids":["31535751"],"confidence":"Low","gaps":["Indirect mechanism with no direct FUBP1 binding or promoter studies shown","Single lab, not independently confirmed"]},{"year":2020,"claim":"The structural basis of FUSE recognition was resolved, showing all four KH domains independently bind ssDNA with cooperativity needed for high affinity.","evidence":"X-ray crystallography of KH1-4 plus biophysical ssDNA-binding characterization","pmids":["32778776"],"confidence":"High","gaps":["Structures of KH domains bound to physiological FUSE not all captured","How DNA versus RNA selectivity is achieved not fully defined"]},{"year":2020,"claim":"FUBP1's constraint of MYC was refined to a chromatin-level mechanism, showing FUBPs enforce epigenetic setpoints limiting MYC expression.","evidence":"Single-cell MYC tracking and histone-mark ChIP in FUBP knockout MEFs and B-cells","pmids":["33005010"],"confidence":"Medium","gaps":["Mechanism connecting FUSE binding to histone-mark changes not defined","FUBP1 versus FUBP2 individual contributions not separated"]},{"year":2020,"claim":"lncRNA antagonism of FUBP1 was established, showing NORAD sequesters FUBP1 and reduces its nuclear occupancy on pro-apoptotic promoters.","evidence":"RNA pulldown, Co-IP, fractionation, ChIP and xenograft rescue with the NORAD-4 fragment","pmids":["32555178"],"confidence":"Medium","gaps":["Identity of the pro-apoptotic target genes not fully mapped","Quantitative contribution to localization not measured"]},{"year":2020,"claim":"FUBP1 was connected to cell-cycle control through S-phase enrichment and regulation of cyclin A.","evidence":"Cell-cycle synchronization, flow cytometry, qRT-PCR and CRISPR knockout cells","pmids":["32481602"],"confidence":"Low","gaps":["No direct binding to the cyclin A locus shown","Correlative, single-lab evidence"]},{"year":2021,"claim":"A cytoplasmic translational function emerged, showing FUBP1 binds the Nrf2 5'UTR and recruits ribosomes via eIF3η to drive de novo Nrf2 synthesis under oxidative stress.","evidence":"LC-MS/MS, Far Western, RNP-IP, ribosome fractionation and Co-IP with initiation factors","pmids":["33676361"],"confidence":"Medium","gaps":["Structural basis of 5'UTR recognition not defined","Whether translation is cap-dependent or IRES-like unresolved"]},{"year":2021,"claim":"The nuclear import route was identified, with TNPO1 directly importing FUBP1 to enable transcription of immune-checkpoint gene NRP1.","evidence":"Co-IP, nuclear/cytoplasmic fractionation, siRNA knockdown and functional assays","pmids":["33987449"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation for TNPO1 interaction","Direct FUBP1 binding to NRP1 regulatory region not shown"]},{"year":2021,"claim":"FUBP1 was shown to drive cancer stemness by directly activating DVL1 transcription, with its stability controlled by Smurf2 ubiquitination and caspase-3 cleavage.","evidence":"ChIP, luciferase, Co-IP, knockdown/overexpression and in vivo tumor assays in colorectal cancer","pmids":["34288405"],"confidence":"Medium","gaps":["Whether DVL1 activation uses a FUSE-like element not defined","KRAS-dependent degradation switch mechanism incompletely resolved"]},{"year":2023,"claim":"The general splicing-factor model was consolidated, showing FUBP1 stabilizes U2AF2 and SF1 at 3' splice sites to enable splicing of long introns.","evidence":"NMR, crystal structures, in vivo CLIP/interaction data, transcriptional profiling and kinetic modeling","pmids":["37506698"],"confidence":"High","gaps":["How splice-site bridging via U1 snRNP contacts operates not fully resolved","Relationship between FUSE DNA binding and splicing function not integrated"]},{"year":2023,"claim":"lncRNA stabilization of FUBP1 was demonstrated in immune cells, where NR_109 competes with JTV-1 for the FUBP1 C-terminus to block its degradation and sustain c-Myc activation.","evidence":"Co-IP, RNA-IP, ubiquitination assays, rescue experiments and in vivo tumor models","pmids":["37217247"],"confidence":"Medium","gaps":["JTV-1 as the relevant E3-linked degron adaptor not fully characterized","Direct versus indirect c-Myc activation not separated"]},{"year":2024,"claim":"A new transcriptional axis was defined in which FUBP1 directly activates USP29, which stabilizes AURKB to promote gastric cancer.","evidence":"ChIP, luciferase, Co-IP, ubiquitination assay, mass spectrometry and xenograft model","pmids":["38233848"],"confidence":"Medium","gaps":["Whether USP29 activation uses a FUSE-like element not shown","Single-lab, single-cancer-type validation"]},{"year":2025,"claim":"FUBP1 was established as a reader of 2'-O-methylated RNA that directs Nm-dependent splicing, linking it mechanistically to RNA modification biology.","evidence":"Affinity purification/MS, EMSA, caRNA Nm profiling, occupancy profiling and splicing analysis upon depletion","pmids":["41105785"],"confidence":"High","gaps":["Structural basis of Nm preference not resolved","How Nm reading is integrated with U2AF2/SF1 stabilization unknown"]},{"year":2025,"claim":"Dual transcriptional and splicing control of a single lncRNA locus was demonstrated, with FUBP1 both enhancing transcription via a FUSE-like sequence and facilitating splicing via U-rich intronic binding.","evidence":"ChIP, RNA-IP, minigene splicing assays and knockdown in the context of SPA lncRNA and PWS bodies","pmids":["40147944"],"confidence":"Medium","gaps":["Functional consequence of FUBP1 enrichment in PWS bodies unknown","How transcriptional and splicing roles are coordinated unresolved"]},{"year":2025,"claim":"FUBP1 was implicated in miRNA strand-selective processing, supporting miR-155-3p maturation in macrophages.","evidence":"RNA-binding protein knockdown with strand-selective miRNA quantification","pmids":["40825800"],"confidence":"Low","gaps":["Direct binding to pre-miR-155 not shown","Mechanism of strand selection not defined"]},{"year":null,"claim":"It remains unresolved how FUBP1's distinct activities — FUSE-DNA transcriptional control, 3' splice-site stabilization, Nm/m6A RNA reading, and 5'UTR translational activation — are partitioned and coordinated within a single protein across subcellular compartments and cell states.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating DNA-binding and RNA-binding functions","Determinants of nuclear versus cytoplasmic activity not defined","Substrate/target selection rules across contexts unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,9,10]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,2,3,5,11]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[24,12,21,7]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[11]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[19,20,1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[11,19]},{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,5,2,3]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[24,7,12,21]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[12,21,13,18]}],"complexes":[],"partners":["U2AF2","SF1","RUNX1","EIF3","TNPO1","USP29"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96AE4","full_name":"Far upstream element-binding protein 1","aliases":["DNA helicase V","hDH V"],"length_aa":644,"mass_kda":67.6,"function":"Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q96AE4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FUBP1","classification":"Not Classified","n_dependent_lines":122,"n_total_lines":1208,"dependency_fraction":0.10099337748344371},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/FUBP1","total_profiled":1310},"omim":[{"mim_id":"612082","title":"CAPICUA TRANSCRIPTIONAL REPRESSOR; CIC","url":"https://www.omim.org/entry/612082"},{"mim_id":"604819","title":"POLY-U-BINDING SPLICING FACTOR, 60-KD; PUF60","url":"https://www.omim.org/entry/604819"},{"mim_id":"603536","title":"FAR UPSTREAM ELEMENT-BINDING PROTEIN 3; FUBP3","url":"https://www.omim.org/entry/603536"},{"mim_id":"603445","title":"KH-TYPE SPLICING REGULATORY PROTEIN; KHSRP","url":"https://www.omim.org/entry/603445"},{"mim_id":"603444","title":"FAR UPSTREAM ELEMENT-BINDING PROTEIN 1; FUBP1","url":"https://www.omim.org/entry/603444"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FUBP1"},"hgnc":{"alias_symbol":["FBP"],"prev_symbol":["FUBP"]},"alphafold":{"accession":"Q96AE4","domains":[{"cath_id":"3.30.1370.10","chopping":"100-170","consensus_level":"high","plddt":89.0917,"start":100,"end":170},{"cath_id":"3.30.1370.10","chopping":"185-265","consensus_level":"high","plddt":80.5046,"start":185,"end":265},{"cath_id":"3.30.1370.10","chopping":"276-347","consensus_level":"high","plddt":86.5125,"start":276,"end":347},{"cath_id":"3.30.1370.10","chopping":"376-452","consensus_level":"high","plddt":82.5971,"start":376,"end":452}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96AE4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96AE4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96AE4-F1-predicted_aligned_error_v6.png","plddt_mean":63.59},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FUBP1","jax_strain_url":"https://www.jax.org/strain/search?query=FUBP1"},"sequence":{"accession":"Q96AE4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96AE4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96AE4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96AE4"}},"corpus_meta":[{"pmid":"22869205","id":"PMC_22869205","title":"Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.","date":"2012","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/22869205","citation_count":463,"is_preprint":false},{"pmid":"21817013","id":"PMC_21817013","title":"Mutations in CIC and FUBP1 contribute to human oligodendroglioma.","date":"2011","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/21817013","citation_count":422,"is_preprint":false},{"pmid":"22588899","id":"PMC_22588899","title":"CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas.","date":"2012","source":"Acta neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/22588899","citation_count":115,"is_preprint":false},{"pmid":"34274028","id":"PMC_34274028","title":"LCAT3, a novel m6A-regulated long non-coding RNA, plays an oncogenic role in lung cancer via binding with FUBP1 to activate c-MYC.","date":"2021","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34274028","citation_count":112,"is_preprint":false},{"pmid":"34116677","id":"PMC_34116677","title":"The circACTN4 interacts with FUBP1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC.","date":"2021","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34116677","citation_count":84,"is_preprint":false},{"pmid":"27157613","id":"PMC_27157613","title":"MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1.","date":"2016","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/27157613","citation_count":74,"is_preprint":false},{"pmid":"37217247","id":"PMC_37217247","title":"The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development.","date":"2023","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/37217247","citation_count":70,"is_preprint":false},{"pmid":"30343319","id":"PMC_30343319","title":"The master regulator FUBP1: its emerging role in normal cell function and malignant development.","date":"2018","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/30343319","citation_count":67,"is_preprint":false},{"pmid":"25212137","id":"PMC_25212137","title":"Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins.","date":"2011","source":"Food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25212137","citation_count":67,"is_preprint":false},{"pmid":"24030748","id":"PMC_24030748","title":"Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors.","date":"2013","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/24030748","citation_count":48,"is_preprint":false},{"pmid":"26545048","id":"PMC_26545048","title":"Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1.","date":"2015","source":"CNS oncology","url":"https://pubmed.ncbi.nlm.nih.gov/26545048","citation_count":47,"is_preprint":false},{"pmid":"38443680","id":"PMC_38443680","title":"tiRNA-Val-CAC-2 interacts with FUBP1 to promote pancreatic cancer metastasis by activating c‑MYC transcription.","date":"2024","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/38443680","citation_count":45,"is_preprint":false},{"pmid":"34288405","id":"PMC_34288405","title":"FUBP1 promotes colorectal cancer stemness and metastasis via DVL1-mediated activation of Wnt/β-catenin signaling.","date":"2021","source":"Molecular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34288405","citation_count":44,"is_preprint":false},{"pmid":"19003864","id":"PMC_19003864","title":"2-D DIGE profiling of hepatocellular carcinoma tissues identified isoforms of far upstream binding protein (FUBP) as novel candidates in liver carcinogenesis.","date":"2008","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/19003864","citation_count":44,"is_preprint":false},{"pmid":"24117486","id":"PMC_24117486","title":"Loss of FUBP1 expression in gliomas predicts FUBP1 mutation and is associated with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of heterozygosity.","date":"2014","source":"Neuropathology and applied neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/24117486","citation_count":42,"is_preprint":false},{"pmid":"24798327","id":"PMC_24798327","title":"The splicing factor FUBP1 is required for the efficient splicing of oncogene MDM2 pre-mRNA.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24798327","citation_count":35,"is_preprint":false},{"pmid":"26095368","id":"PMC_26095368","title":"Single-Stranded DNA-Binding Transcriptional Regulator FUBP1 Is Essential for Fetal and Adult Hematopoietic Stem Cell Self-Renewal.","date":"2015","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26095368","citation_count":34,"is_preprint":false},{"pmid":"30500954","id":"PMC_30500954","title":"Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation.","date":"2018","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/30500954","citation_count":34,"is_preprint":false},{"pmid":"23527265","id":"PMC_23527265","title":"A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23527265","citation_count":32,"is_preprint":false},{"pmid":"31553912","id":"PMC_31553912","title":"Identification of FUBP1 as a Long Tail Cancer Driver and Widespread Regulator of Tumor Suppressor and Oncogene Alternative Splicing.","date":"2019","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/31553912","citation_count":31,"is_preprint":false},{"pmid":"37506698","id":"PMC_37506698","title":"FUBP1 is a general splicing factor facilitating 3' splice site recognition and splicing of long introns.","date":"2023","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/37506698","citation_count":30,"is_preprint":false},{"pmid":"25662218","id":"PMC_25662218","title":"FUBP1: a new protagonist in splicing regulation of the DMD gene.","date":"2015","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/25662218","citation_count":30,"is_preprint":false},{"pmid":"28076379","id":"PMC_28076379","title":"Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma.","date":"2017","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28076379","citation_count":30,"is_preprint":false},{"pmid":"26490982","id":"PMC_26490982","title":"Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26490982","citation_count":27,"is_preprint":false},{"pmid":"32555178","id":"PMC_32555178","title":"NORAD orchestrates endometrial cancer progression by sequestering FUBP1 nuclear localization to promote cell apoptosis.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/32555178","citation_count":27,"is_preprint":false},{"pmid":"31511046","id":"PMC_31511046","title":"FUBP1 promotes neuroblastoma proliferation via enhancing glycolysis-a new possible marker of malignancy for neuroblastoma.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/31511046","citation_count":23,"is_preprint":false},{"pmid":"36932454","id":"PMC_36932454","title":"circMMD reduction following tumor treating fields inhibits glioblastoma progression through FUBP1/FIR/DVL1 and miR-15b-5p/FZD6 signaling.","date":"2023","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/36932454","citation_count":22,"is_preprint":false},{"pmid":"24192769","id":"PMC_24192769","title":"Far upstream element-binding protein 1 (FUBP1) is overexpressed in human gastric cancer tissue compared to non-cancerous tissue.","date":"2013","source":"Onkologie","url":"https://pubmed.ncbi.nlm.nih.gov/24192769","citation_count":22,"is_preprint":false},{"pmid":"30635626","id":"PMC_30635626","title":"The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia.","date":"2019","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/30635626","citation_count":19,"is_preprint":false},{"pmid":"29031818","id":"PMC_29031818","title":"Camptothecin and its analog SN-38, the active metabolite of irinotecan, inhibit binding of the transcriptional regulator and oncoprotein FUBP1 to its DNA target sequence FUSE.","date":"2017","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29031818","citation_count":19,"is_preprint":false},{"pmid":"29743362","id":"PMC_29743362","title":"Adenovirus 5 E1A-Mediated Suppression of p53 via FUBP1.","date":"2018","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/29743362","citation_count":18,"is_preprint":false},{"pmid":"36086966","id":"PMC_36086966","title":"FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1.","date":"2022","source":"Allergologia et immunopathologia","url":"https://pubmed.ncbi.nlm.nih.gov/36086966","citation_count":17,"is_preprint":false},{"pmid":"30871777","id":"PMC_30871777","title":"Fubp1 supports the lactate-Akt-mTOR axis through the upregulation of Hk1 and Hk2.","date":"2019","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/30871777","citation_count":15,"is_preprint":false},{"pmid":"33676361","id":"PMC_33676361","title":"Far Upstream Binding Protein 1 (FUBP1) participates in translational regulation of Nrf2 protein under oxidative stress.","date":"2021","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/33676361","citation_count":15,"is_preprint":false},{"pmid":"33005010","id":"PMC_33005010","title":"FUBP1 and FUBP2 enforce distinct epigenetic setpoints for MYC expression in primary single murine cells.","date":"2020","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/33005010","citation_count":14,"is_preprint":false},{"pmid":"33987449","id":"PMC_33987449","title":"TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer.","date":"2021","source":"Journal of immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/33987449","citation_count":14,"is_preprint":false},{"pmid":"25030436","id":"PMC_25030436","title":"Far upstream element-binding protein 1(FUBP1) expression differs between human colorectal cancer and non-cancerous tissue.","date":"2014","source":"Neoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/25030436","citation_count":12,"is_preprint":false},{"pmid":"38233848","id":"PMC_38233848","title":"USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer.","date":"2024","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/38233848","citation_count":11,"is_preprint":false},{"pmid":"28301294","id":"PMC_28301294","title":"FUBP/KH domain proteins in transcription: Back to the future.","date":"2017","source":"Transcription","url":"https://pubmed.ncbi.nlm.nih.gov/28301294","citation_count":10,"is_preprint":false},{"pmid":"32481602","id":"PMC_32481602","title":"Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival.","date":"2020","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/32481602","citation_count":10,"is_preprint":false},{"pmid":"35546072","id":"PMC_35546072","title":"Far upstream element -binding protein 1 (FUBP1) participates in the malignant process and glycolysis of colon cancer cells by combining with c-Myc.","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/35546072","citation_count":10,"is_preprint":false},{"pmid":"36394649","id":"PMC_36394649","title":"A circular RNA, circPTPN14, increases MYC transcription by interacting with FUBP1 and exacerbates renal fibrosis.","date":"2022","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/36394649","citation_count":10,"is_preprint":false},{"pmid":"39067088","id":"PMC_39067088","title":"FUBP1 in human cancer: Characteristics, functions, and potential applications.","date":"2024","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39067088","citation_count":9,"is_preprint":false},{"pmid":"33649780","id":"PMC_33649780","title":"FUBP1 mediates the growth and metastasis through TGFβ/Smad signaling in pancreatic adenocarcinoma.","date":"2021","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33649780","citation_count":8,"is_preprint":false},{"pmid":"33138041","id":"PMC_33138041","title":"Developmental Roles of FUSE Binding Protein 1 (Fubp1) in Tooth Morphogenesis.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33138041","citation_count":8,"is_preprint":false},{"pmid":"27729195","id":"PMC_27729195","title":"Pyrazolo[1,5a]pyrimidines as a new class of FUSE binding protein 1 (FUBP1) inhibitors.","date":"2016","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27729195","citation_count":7,"is_preprint":false},{"pmid":"32778776","id":"PMC_32778776","title":"Comparative structural analyses and nucleotide-binding characterization of the four KH domains of FUBP1.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32778776","citation_count":7,"is_preprint":false},{"pmid":"30653565","id":"PMC_30653565","title":"FUSE binding protein 1 (FUBP1) expression is upregulated by T-cell acute lymphocytic leukemia protein 1 (TAL1) and required for efficient erythroid differentiation.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30653565","citation_count":6,"is_preprint":false},{"pmid":"34712553","id":"PMC_34712553","title":"Long non-coding RNA KRT8P41/miR-193a-3p/FUBP1 axis modulates the proliferation and invasion of chordoma cells.","date":"2021","source":"Journal of bone oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34712553","citation_count":5,"is_preprint":false},{"pmid":"31535751","id":"PMC_31535751","title":"CRISPR/Cas-mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein via downregulating Syncrip expression.","date":"2019","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/31535751","citation_count":5,"is_preprint":false},{"pmid":"36382923","id":"PMC_36382923","title":"Discovery of Anthranilic Acid Derivatives as Difluoromethylornithine Adjunct Agents That Inhibit Far Upstream Element Binding Protein 1 (FUBP1) Function.","date":"2022","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/36382923","citation_count":5,"is_preprint":false},{"pmid":"28588622","id":"PMC_28588622","title":"Delayed Mesoderm and Erythroid Differentiation of Murine Embryonic Stem Cells in the Absence of the Transcriptional Regulator FUBP1.","date":"2017","source":"Stem cells international","url":"https://pubmed.ncbi.nlm.nih.gov/28588622","citation_count":5,"is_preprint":false},{"pmid":"37932299","id":"PMC_37932299","title":"Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37932299","citation_count":4,"is_preprint":false},{"pmid":"34872893","id":"PMC_34872893","title":"Effect of RNA Interference Inhibiting the Expression of the FUBP1 Gene on Biological Function of Gastric Cancer Cell Line SGC7901.","date":"2021","source":"The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/34872893","citation_count":3,"is_preprint":false},{"pmid":"40685790","id":"PMC_40685790","title":"Epigenetic Activation of CCDC183-AS1 Promotes Osteoclastogenesis and Prostate Cancer Bone Metastasis Through the FUBP1/LIGHT Axis.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40685790","citation_count":2,"is_preprint":false},{"pmid":"37715422","id":"PMC_37715422","title":"The expression and clinical value of LRP11, FUBP1 and TET1 in cervical cancer.","date":"2023","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/37715422","citation_count":2,"is_preprint":false},{"pmid":"33954195","id":"PMC_33954195","title":"Differentially Expressed Long Noncoding RNAs Involved in FUBP1 Promoting Hepatocellular Carcinoma Cells Proliferation.","date":"2021","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/33954195","citation_count":2,"is_preprint":false},{"pmid":"37014433","id":"PMC_37014433","title":"circPTPN14 promotes renal fibrosis through its interaction with FUBP1 to enhance MYC transcription.","date":"2023","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/37014433","citation_count":2,"is_preprint":false},{"pmid":"41105785","id":"PMC_41105785","title":"Nuclear 2'-O-methylation regulates RNA splicing through its binding protein FUBP1.","date":"2025","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/41105785","citation_count":1,"is_preprint":false},{"pmid":"40965935","id":"PMC_40965935","title":"PTBP1 Reduces KLF9 mRNA Stability and Upregulates FUBP1 to Promote Colorectal Cancer Stemness and Cisplatin Resistance.","date":"2025","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/40965935","citation_count":1,"is_preprint":false},{"pmid":"40147944","id":"PMC_40147944","title":"A dual effect of FUBP1 on SPA lncRNA maturation.","date":"2025","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/40147944","citation_count":1,"is_preprint":false},{"pmid":"40580249","id":"PMC_40580249","title":"Regulatory RNA network mediated by FUBP1 drives the proliferation and invasion of triple-negative breast cancer cells.","date":"2025","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/40580249","citation_count":1,"is_preprint":false},{"pmid":"40825800","id":"PMC_40825800","title":"The regulation of miR-155 strand selection by CELF2, FUBP1 and KSRP proteins.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40825800","citation_count":1,"is_preprint":false},{"pmid":"42223720","id":"PMC_42223720","title":"The RNA-binding protein RBFOX2 suppresses colorectal cancer proliferation and metastasis by reducing FUBP1 mRNA stability to induce mitochondrial dysfunction and ferroptosis.","date":"2026","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/42223720","citation_count":0,"is_preprint":false},{"pmid":"42166100","id":"PMC_42166100","title":"JARID1B-Mediated H3K4me3 Demethylation Promotes Cisplatin Resistance in Oral Squamous Cell Carcinoma Cells via the miR-495-3p/FUBP1 Axis.","date":"2026","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/42166100","citation_count":0,"is_preprint":false},{"pmid":"42000079","id":"PMC_42000079","title":"Antiviral activity of novel chemical compound 0411, derived from FUBP1-IN-1 against hepatitis B virus by upregulation of DUSP5.","date":"2026","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/42000079","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.18.670784","title":"<i>VILMIR</i>  is a  <i>trans</i>  -acting long noncoding RNA that enhances the host interferon response in human epithelial cells","date":"2025-08-22","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.18.670784","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.20.649728","title":"Nuclear 2′-O-methylation regulates RNA splicing through its binding protein FUBP1","date":"2025-04-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.20.649728","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.05.641704","title":"The strand-selective regulation of miR-155 in response to lipopolysaccharide by CELF2, FUBP1 and KSRP proteins","date":"2025-03-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.05.641704","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.06.651696","title":"Disruption of Microhomology-mediated End-joining in Ewing Sarcoma","date":"2025-05-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.06.651696","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.10.637450","title":"Dissecting the role of RNA-binding proteins in early herpes simplex virus 1 transcription using acute protein depletion","date":"2025-02-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.10.637450","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":37895,"output_tokens":6604,"usd":0.106372,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":15504,"output_tokens":6856,"usd":0.12446,"stage2_stop_reason":"end_turn"},"total_usd":0.230832,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"FUBP1 is a general splicing factor that binds a novel cis-regulatory motif and stabilizes U2AF2 and SF1 (key 3' splice site components) through multivalent binding interfaces in its disordered regions; it is required for efficient splicing of long introns (representing ~80% of human introns) and interacts with U1 snRNP-associated proteins, suggesting a role in splice site bridging. NMR, structural, and in vivo interaction data, plus transcriptional profiling and kinetic modeling, support this model.\",\n      \"method\": \"NMR, crystal structures, in vivo CLIP/interaction data, transcriptional profiling, kinetic modeling, mutagenesis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal methods (NMR, structural data, in vivo interaction, transcriptional profiling, kinetic modeling) in a single rigorous study\",\n      \"pmids\": [\"37506698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Crystal structures of all four KH domains (KH1–4) of FUBP1 show they are highly conserved topologically and each can independently bind the FUSE ssDNA sequence; KH3 shows higher nucleotide-binding potency; differences in amino acid composition at the binding cleft account for diverse nucleotide-sequence preferences among KH1–4; cooperativity of all four KH modules is required for nanomolar-affinity FUSE binding.\",\n      \"method\": \"X-ray crystallography, ssDNA-binding characterization (biophysical assays)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structures of all four KH domains plus binding characterization in a single rigorous paper\",\n      \"pmids\": [\"32778776\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FUBP1 binds discrete cis-regulatory elements within intron 11 of MDM2 pre-mRNA and acts as a positive splicing regulator; blocking FUBP1 function in in vitro splicing reactions decreased splicing efficiency, and FUBP1 knockdown in cells induced formation of the stress-induced MDM2-ALT1 splice variant under normal conditions.\",\n      \"method\": \"In vitro splicing assays, RNA binding assays, siRNA knockdown, minigene splicing reporter\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro splicing reconstitution plus cell-based knockdown with defined molecular phenotype in a single study\",\n      \"pmids\": [\"24798327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"FUBP1 promotes constitutive inclusion of DMD exon 39 by binding a functional intronic splicing enhancer (ISE) in intron 38; binding was established by RNA pulldown, RNA EMSA, and RNA-ChIP on endogenous DMD pre-mRNA; serial deletion and mutagenesis of minigenes delineated the functional ISE.\",\n      \"method\": \"RNA pulldown, RNA EMSA, RNA-ChIP, minigene deletion/mutagenesis analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal in vitro and in-cell methods including mutagenesis and ChIP on endogenous pre-mRNA\",\n      \"pmids\": [\"25662218\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FUBP1 participates in regulating N6-methyladenosine (m6A) RNA methylation; its loss leads to global changes in RNA splicing and widespread expression of aberrant driver isoforms, as demonstrated by an in vivo CRISPR screen identifying FUBP1 as a long-tail tumor suppressor that cooperates with other tumor suppressor genes to transform mammary epithelial cells.\",\n      \"method\": \"In vivo CRISPR screen, RNA splicing profiling, m6A methylation analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo CRISPR screen plus splicing/m6A profiling, single lab, two orthogonal approaches\",\n      \"pmids\": [\"31553912\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FUBP1 is an Nm (2'-O-methylation) RNA-binding protein: EMSA validated preference of FUBP1 for Nm-modified RNA; FUBP1 predominantly binds intronic regions; Nm sites in chromatin-associated RNA (caRNA) overlap with FUBP1-binding sites; Nm depletion reduced FUBP1 occupancy on modified regions; FUBP1 depletion induced exon skipping in Nm-modified genes, establishing FUBP1 as a mediator of Nm-dependent splicing regulation.\",\n      \"method\": \"RNA affinity purification/mass spectrometry, EMSA, caRNA Nm profiling, ChIP-seq/CLIP, siRNA depletion with splicing analysis\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal biochemical and genomic methods (EMSA, affinity purification/MS, occupancy profiling, splicing analysis upon depletion) in a single study\",\n      \"pmids\": [\"41105785\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"FUBP1 is essential for fetal and adult hematopoietic stem cell (HSC) self-renewal; conditional functional inactivation in two mouse models caused embryonic lethal anemia (~E15.5) with severely diminished HSCs; FUBP1-deficient HSCs showed intrinsic defects in maintenance and long-term reconstitution, with upregulation of cell-cycle inhibitor p21 and pro-apoptotic Noxa, leading to increased generation time and HSC death tracked by video-microscopy.\",\n      \"method\": \"Conditional knockout mouse models (two independent models), transplantation assays, video-microscopy cell tracking, transcriptional analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two independent mouse KO models, multiple cellular and molecular readouts, replicated phenotype\",\n      \"pmids\": [\"26095368\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"RUNX1 and FUBP1 interact in the same transcriptional regulatory complex in human B-cell precursor lymphoblasts and co-occupy active chromatin at the c-KIT locus, including a novel FUBP1 FUSE-like binding sequence at +30 kb enhancer; FUBP1 and RUNX1 cooperate to upregulate c-KIT expression, promoting cell proliferation and resistance to imatinib.\",\n      \"method\": \"Co-immunoprecipitation, ChIP-seq, enhancer characterization, luciferase reporter, functional proliferation assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, ChIP-seq, functional reporter and proliferation assays, multiple orthogonal methods in single study\",\n      \"pmids\": [\"30500954\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FUBP1 is a novel binding partner of adenovirus 5 E1A; FUBP1 binds directly to E1A via its N-terminus (residues 1–82) and conserved region 3 (residues 139–204); FUBP1 depletion reduces virus growth and activates p53-regulated genes; during infection FUBP1 is relocalized within the nucleus, recruited to viral promoters with E1A while lost from the FUSE upstream of c-Myc; FUBP1 suppresses p53 DNA binding, and E1A stabilizes the FUBP1-p53 complex to prevent p53 promoter binding.\",\n      \"method\": \"Co-immunoprecipitation, siRNA depletion, ChIP, gene expression analysis, domain mapping\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding mapped to domains, ChIP relocalization data, functional p53 and viral growth readouts in a single study\",\n      \"pmids\": [\"29743362\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Camptothecin (CPT) and its derivative SN-38 (active irinotecan metabolite) inhibit FUBP1 activity by preventing FUBP1 binding to its single-stranded DNA target FUSE in vitro, and induce deregulation of FUBP1 target genes in HCC cells.\",\n      \"method\": \"In vitro DNA binding assay (FUBP1/FUSE interaction), gene expression analysis in HCC cells, drug library screen\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro biochemical assay demonstrating inhibition of FUBP1-FUSE interaction, plus cell-based gene expression, single lab\",\n      \"pmids\": [\"29031818\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Pyrazolo[1,5a]pyrimidine-based compounds (e.g., compound 6) inhibit FUBP1 binding to its single-stranded DNA target FUSE with IC50 of 11.0 μM in biophysical assays, and reduce expansion and induce death in hepatocellular carcinoma cells.\",\n      \"method\": \"Biophysical binding assay (FUBP1-FUSE interaction), cell viability assay, medium-throughput screening\",\n      \"journal\": \"Bioorganic & medicinal chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — biochemical FUSE binding assay with IC50, cell-based validation, single lab and single study\",\n      \"pmids\": [\"27729195\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FUBP1 binds the Nrf2 5'UTR in response to H2O2 (identified by LC-MS/MS, Far Western blot, and RNP-IP); FUBP1 undergoes cytosolic redistribution to ribosomal fractions under oxidative stress; FUBP1 gains physical interaction with eIF3η (but not eIF4E, eIF2α, or eIF1) upon H2O2 treatment; FUBP1 promotes 40S ribosomal subunit attachment to Nrf2 mRNA and 43S pre-initiation complex formation, facilitating de novo Nrf2 protein translation under oxidative stress.\",\n      \"method\": \"LC-MS/MS, Far Western blot, RNP-immunoprecipitation, ribosome fractionation, siRNA knockdown, co-immunoprecipitation with translation initiation factors\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biochemical methods (LC-MS/MS, Far Western, RNP-IP, fractionation, Co-IP), single lab\",\n      \"pmids\": [\"33676361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FUBP1 promotes colorectal cancer stemness and metastasis by directly binding to the DVL1 promoter to activate DVL1 transcription, thereby activating Wnt/β-catenin signaling and increasing pluripotent transcription factors (c-Myc, NANOG, SOX2); FUBP1 protein stability is regulated by Smurf2-mediated ubiquitin degradation (reduced in KRAS-wild-type CRC) and by caspase-3-dependent cleavage (reduced in KRAS-mutant CRC).\",\n      \"method\": \"ChIP, luciferase reporter, co-immunoprecipitation, overexpression/knockdown, in vitro and in vivo tumor assays\",\n      \"journal\": \"Molecular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and luciferase for direct promoter binding, Co-IP for protein interactions, in vivo validation, single lab\",\n      \"pmids\": [\"34288405\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FUBP1 inhibits HIF1α degradation by downregulating VHL (the E3 ligase for HIF1α), resulting in upregulation of LDHB and enhanced glycolysis in neuroblastoma cells; this pro-glycolytic mechanism is independent of N-Myc regulation.\",\n      \"method\": \"Luciferase assay, Western blot, ChIP, ELISA for glycolytic metabolites, siRNA knockdown\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — ChIP and luciferase for target gene regulation, multiple metabolic readouts, single lab\",\n      \"pmids\": [\"31511046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Fubp1 upregulates mRNA levels of hexokinase genes Hk1 and Hk2, supporting aerobic glycolysis and the lactate-Akt-mTOR survival axis in cells; Fubp1 deficiency reduces Hk1/Hk2 expression.\",\n      \"method\": \"qRT-PCR, Western blot, cell survival assays, metabolic assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, expression-level analysis with limited mechanistic depth, no direct binding/ChIP shown\",\n      \"pmids\": [\"30871777\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"FUBP1 protein level is enriched in S phase; FUBP1 deficiency alters cell cycle progression in S phase by downregulating Ccna (cyclin A) mRNA expression; FUBP1 deficiency also confers survival advantages against metabolic stress and anti-cancer drugs.\",\n      \"method\": \"Cell cycle synchronization, flow cytometry, qRT-PCR, Western blot, CRISPR/Cas9 KO cells\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, correlation between Fubp1 and cyclin A without direct binding demonstrated, limited mechanistic depth\",\n      \"pmids\": [\"32481602\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CRISPR/Cas9-mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein; Fubp1 upregulates Syncrip (main post-transcriptional regulator of Per1 protein oscillation) at mRNA and protein levels, establishing a Fubp1-Syncrip-Per1 regulatory axis for circadian clock maintenance.\",\n      \"method\": \"CRISPR/Cas9 knockout, qRT-PCR, Western blot, circadian oscillation profiling\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect mechanism (Fubp1→Syncrip→Per1) without direct binding or promoter studies shown\",\n      \"pmids\": [\"31535751\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TAL1 directly activates the FUBP1 promoter in erythroid progenitor cells, requiring an intact GATA sequence in a combined E-box/GATA motif; this TAL1-driven FUBP1 expression is required for efficient erythroid differentiation, as FUBP1-deficient progenitors show limited erythroid differentiation capacity.\",\n      \"method\": \"ChIP, promoter reporter assays, FUBP1 knockdown, erythroid differentiation assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ChIP showing TAL1 binding to FUBP1 promoter, mutagenesis of binding motif, functional differentiation assay, single lab\",\n      \"pmids\": [\"30653565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FUBP1 is required for NR_109 lncRNA-mediated M2-like macrophage polarization; NR_109 competes with JVT-1 (JTV-1) to bind the C-terminus domain of FUBP1, preventing ubiquitin-mediated degradation of FUBP1, thereby stabilizing FUBP1 and enabling c-Myc transcription activation.\",\n      \"method\": \"Co-immunoprecipitation, RNA immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vivo tumor models\",\n      \"journal\": \"Journal for immunotherapy of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP for protein interaction, ubiquitination assay, functional rescue experiments, single lab\",\n      \"pmids\": [\"37217247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TNPO1 (Transportin-1) mediates nuclear import of FUBP1 through direct interaction; nuclear FUBP1 regulates transcription of the immune checkpoint gene NRP1; knockdown of FUBP1 inhibits cervical cancer cell proliferation and migration.\",\n      \"method\": \"Co-immunoprecipitation, nuclear/cytoplasmic fractionation, siRNA knockdown, functional assays\",\n      \"journal\": \"Journal of immunology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP for TNPO1-FUBP1 interaction, fractionation data, limited mechanistic follow-up for NRP1 regulation, single lab\",\n      \"pmids\": [\"33987449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NORAD lncRNA binds the central domain of FUBP1 through multiple regions and attenuates FUBP1 nuclear localization, impairing FUBP1 occupancy on pro-apoptotic gene promoters and thereby inducing apoptosis in endometrial cancer cells; the NORAD-4 fragment sufficient for FUBP1 binding recapitulated the anti-tumor effects in vivo.\",\n      \"method\": \"RNA pulldown, co-immunoprecipitation, subcellular fractionation/localization, ChIP, xenograft model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal methods (RNA pulldown, Co-IP, fractionation, ChIP, in vivo rescue), single lab\",\n      \"pmids\": [\"32555178\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FUBP1 directly activates USP29 gene transcription (demonstrated by ChIP and luciferase assay); USP29 in turn interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis promoting gastric cancer.\",\n      \"method\": \"ChIP, luciferase reporter, Co-IP, ubiquitination assay, mass spectrometry, qRT-PCR, xenograft model\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and luciferase for FUBP1 transcriptional activation of USP29, Co-IP and ubiquitination assay for USP29-AURKB axis, single lab\",\n      \"pmids\": [\"38233848\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FUBP1 protein binds the EV71 5'-UTR (an IRES element) as shown by RNA affinity pulldown coupled with LC-MS/MS; kaempferol treatment changes the composition of IRES-associated trans-acting factors including FUBP1, affecting IRES function and EV71 replication.\",\n      \"method\": \"RNA affinity pull-down, LC-MS/MS\",\n      \"journal\": \"Food chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown/MS experiment identifying FUBP1 as IRES-binding protein; minimal mechanistic follow-up for FUBP1 specifically\",\n      \"pmids\": [\"25212137\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FUBP1 promotes SPA lncRNA expression via two distinct mechanisms: (1) enhancing transcription of SPA-embedded polycistronic transcripts by targeting a FUSE-like sequence upstream of the promoter, and (2) facilitating SPA1 splicing and maturation by binding U-rich intronic sequences; both FUBP1 and MYEF2 are enriched in Prader-Willi syndrome (PWS) bodies.\",\n      \"method\": \"ChIP, RNA immunoprecipitation, minigene splicing assays, knockdown with expression analysis, FUSE-like sequence identification\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for transcriptional role, RNA binding and splicing assays, functional knockdown, single lab\",\n      \"pmids\": [\"40147944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"FUBPs enforce epigenetic setpoints that restrict MYC expression; FUBP1/FUBP2-lacking murine embryonic fibroblasts express MYC at levels otherwise attained only after stimulation and show MYC chromatin changes (altered histone marks), establishing that FUBPs constrain MYC expression through chromatin-level regulation in single primary cells.\",\n      \"method\": \"Single-cell MYC expression tracking, chromatin mark profiling (ChIP for histone modifications), FUBP knockout MEFs and B-cells\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single-cell tracking plus ChIP for chromatin marks, multiple cell types, single lab\",\n      \"pmids\": [\"33005010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FUBP1 contributes to miR-155-3p expression/maturation from pre-miR-155 in macrophages; FUBP1 may support miR-155-3p for specific subcellular functions, while KSRP inhibits both miR-155-5p and miR-155-3p maturation without altering relative strand expression.\",\n      \"method\": \"RNA-binding protein knockdown, miRNA quantification, strand-selective miRNA analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, functional knockdown with miRNA measurement but limited mechanistic detail for FUBP1's specific role in processing\",\n      \"pmids\": [\"40825800\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FUBP1 is a multifunctional single-stranded DNA/RNA-binding protein whose four KH domains cooperatively bind the FUSE element to regulate transcription of target genes (most notably c-MYC and p21); it acts as a general splicing factor that stabilizes U2AF2 and SF1 at 3' splice sites to facilitate splicing of long introns, binds intronic cis-regulatory elements to promote exon inclusion (e.g., MDM2, DMD), participates in m6A and 2'-O-methylation-dependent splicing, mediates de novo Nrf2 translation under oxidative stress via interaction with eIF3η and ribosome recruitment, is required for hematopoietic stem cell self-renewal through transcriptional regulation of p21 and pro-apoptotic genes, cooperates with RUNX1 to activate c-KIT enhancer-driven transcription, is imported into the nucleus by TNPO1, and its FUSE-binding activity can be pharmacologically inhibited by camptothecin/SN-38 and small-molecule FUBP1 inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FUBP1 is a multifunctional single-stranded nucleic acid-binding protein that operates as both a transcriptional regulator and a splicing factor, coupling control of gene expression to cell proliferation, hematopoiesis, and cancer [#1, #0, #6]. Its four KH domains are topologically conserved and each independently engages the single-stranded FUSE DNA element, with KH3 showing the highest binding potency and cooperativity among all four modules required for nanomolar-affinity binding [#1]. Through this FUSE-binding activity FUBP1 enforces epigenetic setpoints that restrict MYC expression via chromatin-level regulation, and directly activates additional target promoters including DVL1, USP29, and a FUSE-like enhancer at the c-KIT locus where it cooperates with RUNX1 [#24, #12, #21, #7]. In parallel, FUBP1 functions as a general splicing factor: it binds a cis-regulatory motif and stabilizes the 3' splice site components U2AF2 and SF1 through multivalent interfaces in its disordered regions, enabling efficient splicing of long introns, and it binds discrete intronic enhancer elements to promote exon inclusion in pre-mRNAs such as MDM2 and DMD [#0, #2, #3]. FUBP1 reads RNA modifications, preferentially binding 2'-O-methylated (Nm) intronic RNA to direct Nm-dependent splicing and participating in m6A-linked splicing regulation [#5, #4]. Beyond the nucleus, FUBP1 binds the Nrf2 5'UTR under oxidative stress, interacts with eIF3\\u03b7, and recruits the 40S ribosomal subunit to promote de novo Nrf2 translation [#11]. FUBP1 is essential for fetal and adult hematopoietic stem cell self-renewal, its loss causing embryonic lethal anemia and HSC death through upregulation of p21 and the pro-apoptotic gene Noxa [#6]. FUBP1 abundance and localization are themselves controlled by ubiquitin-mediated degradation, TNPO1-dependent nuclear import, and antagonistic lncRNAs (NORAD, NR_109) [#18, #19, #20]. Its FUSE-binding activity is pharmacologically inhibited by camptothecin/SN-38 and by pyrazolo[1,5a]pyrimidine compounds [#9, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Identifying FUBP1 among viral IRES-associated factors raised the question of whether FUBP1 engages structured 5'UTR RNA elements beyond its DNA-binding role.\",\n      \"evidence\": \"RNA affinity pulldown coupled with LC-MS/MS on the EV71 5'-UTR IRES\",\n      \"pmids\": [\"25212137\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single pulldown/MS experiment with no functional follow-up specific to FUBP1\", \"Direct binding versus complex co-purification not distinguished\", \"No mechanism for IRES regulation established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether FUBP1 acted on pre-mRNA splicing was addressed by showing it binds intronic cis-elements and positively regulates a defined splicing event.\",\n      \"evidence\": \"In vitro splicing reconstitution, RNA binding, and siRNA knockdown with MDM2 minigene reporters\",\n      \"pmids\": [\"24798327\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of how binding promotes splicing not defined\", \"Generality across other transcripts not established\", \"Spliceosomal contacts not identified\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"FUBP1's role as a sequence-specific intronic splicing enhancer factor was extended by demonstrating it drives constitutive exon inclusion through an endogenous ISE.\",\n      \"evidence\": \"RNA pulldown, RNA EMSA, RNA-ChIP and minigene mutagenesis on DMD pre-mRNA\",\n      \"pmids\": [\"25662218\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How ISE binding recruits the splicing machinery unresolved\", \"Whether the same mechanism operates genome-wide unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"The physiological requirement for FUBP1 was established by showing it is intrinsically required for hematopoietic stem cell self-renewal, linking its molecular activity to a developmental phenotype.\",\n      \"evidence\": \"Two independent conditional knockout mouse models, transplantation, video-microscopy, and transcriptional analysis\",\n      \"pmids\": [\"26095368\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether p21/Noxa regulation is direct transcriptional binding not shown\", \"Splicing versus transcriptional contribution to the phenotype not separated\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The therapeutic tractability of FUBP1 was probed by identifying clinically used drugs that block its DNA-binding activity.\",\n      \"evidence\": \"In vitro FUBP1/FUSE binding assay and gene-expression analysis in HCC cells from a drug library screen\",\n      \"pmids\": [\"29031818\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect inhibition mechanism not resolved\", \"On-target specificity in cells not established\", \"Camptothecin has other primary targets\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Dedicated small-molecule inhibitors were developed to test whether the FUBP1-FUSE interaction is druggable as an anticancer strategy.\",\n      \"evidence\": \"Biophysical FUSE-binding assay with IC50 determination and HCC cell viability assays\",\n      \"pmids\": [\"27729195\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Modest potency (IC50 ~11 \\u00b5M)\", \"Cellular target engagement not confirmed\", \"Selectivity over related KH proteins unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"FUBP1's integration into a defined transcription factor complex was demonstrated by showing it partners with RUNX1 at an enhancer to activate an oncogenic target.\",\n      \"evidence\": \"Reciprocal Co-IP, ChIP-seq, enhancer characterization, luciferase reporters and proliferation assays in B-cell precursors\",\n      \"pmids\": [\"30500954\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct versus bridged RUNX1-FUBP1 contact not mapped\", \"Whether cooperation extends to other enhancers unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"A viral hijacking mechanism revealed FUBP1's regulation of p53, showing adenovirus E1A binds FUBP1 directly via mapped domains and redirects it to suppress p53.\",\n      \"evidence\": \"Co-IP with domain mapping, siRNA depletion, ChIP and gene-expression analysis during infection\",\n      \"pmids\": [\"29743362\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of FUBP1-mediated p53 DNA-binding suppression not defined\", \"Relevance to uninfected cells unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"FUBP1 was placed in RNA-modification biology by an in vivo screen identifying it as a tumor suppressor whose loss reprograms splicing and m6A.\",\n      \"evidence\": \"In vivo CRISPR screen with RNA splicing and m6A profiling in mammary epithelial cells\",\n      \"pmids\": [\"31553912\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct link between FUBP1 and m6A machinery not established\", \"Mechanism connecting FUBP1 loss to aberrant isoforms unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"FUBP1's transcriptional output was shown to be itself transcriptionally controlled by TAL1 during erythroid differentiation, embedding it in a lineage-specific regulatory circuit.\",\n      \"evidence\": \"ChIP, promoter reporter with GATA-motif mutagenesis, knockdown and differentiation assays\",\n      \"pmids\": [\"30653565\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream FUBP1 targets driving differentiation not identified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Multiple studies linked FUBP1 to metabolic reprogramming, indicating it supports glycolysis through regulation of VHL/HIF1\\u03b1 and hexokinase gene expression.\",\n      \"evidence\": \"ChIP, luciferase, metabolite assays in neuroblastoma; qRT-PCR and metabolic assays for Hk1/Hk2\",\n      \"pmids\": [\"31511046\", \"30871777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct promoter binding to Hk1/Hk2 not demonstrated\", \"Mechanism of VHL downregulation not defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"An unexpected role in timekeeping was proposed via a FUBP1-Syncrip-Per1 axis controlling circadian oscillation.\",\n      \"evidence\": \"CRISPR knockout, qRT-PCR, Western blot and circadian profiling\",\n      \"pmids\": [\"31535751\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Indirect mechanism with no direct FUBP1 binding or promoter studies shown\", \"Single lab, not independently confirmed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The structural basis of FUSE recognition was resolved, showing all four KH domains independently bind ssDNA with cooperativity needed for high affinity.\",\n      \"evidence\": \"X-ray crystallography of KH1-4 plus biophysical ssDNA-binding characterization\",\n      \"pmids\": [\"32778776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structures of KH domains bound to physiological FUSE not all captured\", \"How DNA versus RNA selectivity is achieved not fully defined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"FUBP1's constraint of MYC was refined to a chromatin-level mechanism, showing FUBPs enforce epigenetic setpoints limiting MYC expression.\",\n      \"evidence\": \"Single-cell MYC tracking and histone-mark ChIP in FUBP knockout MEFs and B-cells\",\n      \"pmids\": [\"33005010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting FUSE binding to histone-mark changes not defined\", \"FUBP1 versus FUBP2 individual contributions not separated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"lncRNA antagonism of FUBP1 was established, showing NORAD sequesters FUBP1 and reduces its nuclear occupancy on pro-apoptotic promoters.\",\n      \"evidence\": \"RNA pulldown, Co-IP, fractionation, ChIP and xenograft rescue with the NORAD-4 fragment\",\n      \"pmids\": [\"32555178\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the pro-apoptotic target genes not fully mapped\", \"Quantitative contribution to localization not measured\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"FUBP1 was connected to cell-cycle control through S-phase enrichment and regulation of cyclin A.\",\n      \"evidence\": \"Cell-cycle synchronization, flow cytometry, qRT-PCR and CRISPR knockout cells\",\n      \"pmids\": [\"32481602\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct binding to the cyclin A locus shown\", \"Correlative, single-lab evidence\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A cytoplasmic translational function emerged, showing FUBP1 binds the Nrf2 5'UTR and recruits ribosomes via eIF3\\u03b7 to drive de novo Nrf2 synthesis under oxidative stress.\",\n      \"evidence\": \"LC-MS/MS, Far Western, RNP-IP, ribosome fractionation and Co-IP with initiation factors\",\n      \"pmids\": [\"33676361\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of 5'UTR recognition not defined\", \"Whether translation is cap-dependent or IRES-like unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The nuclear import route was identified, with TNPO1 directly importing FUBP1 to enable transcription of immune-checkpoint gene NRP1.\",\n      \"evidence\": \"Co-IP, nuclear/cytoplasmic fractionation, siRNA knockdown and functional assays\",\n      \"pmids\": [\"33987449\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation for TNPO1 interaction\", \"Direct FUBP1 binding to NRP1 regulatory region not shown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"FUBP1 was shown to drive cancer stemness by directly activating DVL1 transcription, with its stability controlled by Smurf2 ubiquitination and caspase-3 cleavage.\",\n      \"evidence\": \"ChIP, luciferase, Co-IP, knockdown/overexpression and in vivo tumor assays in colorectal cancer\",\n      \"pmids\": [\"34288405\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DVL1 activation uses a FUSE-like element not defined\", \"KRAS-dependent degradation switch mechanism incompletely resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The general splicing-factor model was consolidated, showing FUBP1 stabilizes U2AF2 and SF1 at 3' splice sites to enable splicing of long introns.\",\n      \"evidence\": \"NMR, crystal structures, in vivo CLIP/interaction data, transcriptional profiling and kinetic modeling\",\n      \"pmids\": [\"37506698\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How splice-site bridging via U1 snRNP contacts operates not fully resolved\", \"Relationship between FUSE DNA binding and splicing function not integrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"lncRNA stabilization of FUBP1 was demonstrated in immune cells, where NR_109 competes with JTV-1 for the FUBP1 C-terminus to block its degradation and sustain c-Myc activation.\",\n      \"evidence\": \"Co-IP, RNA-IP, ubiquitination assays, rescue experiments and in vivo tumor models\",\n      \"pmids\": [\"37217247\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"JTV-1 as the relevant E3-linked degron adaptor not fully characterized\", \"Direct versus indirect c-Myc activation not separated\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A new transcriptional axis was defined in which FUBP1 directly activates USP29, which stabilizes AURKB to promote gastric cancer.\",\n      \"evidence\": \"ChIP, luciferase, Co-IP, ubiquitination assay, mass spectrometry and xenograft model\",\n      \"pmids\": [\"38233848\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether USP29 activation uses a FUSE-like element not shown\", \"Single-lab, single-cancer-type validation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"FUBP1 was established as a reader of 2'-O-methylated RNA that directs Nm-dependent splicing, linking it mechanistically to RNA modification biology.\",\n      \"evidence\": \"Affinity purification/MS, EMSA, caRNA Nm profiling, occupancy profiling and splicing analysis upon depletion\",\n      \"pmids\": [\"41105785\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of Nm preference not resolved\", \"How Nm reading is integrated with U2AF2/SF1 stabilization unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Dual transcriptional and splicing control of a single lncRNA locus was demonstrated, with FUBP1 both enhancing transcription via a FUSE-like sequence and facilitating splicing via U-rich intronic binding.\",\n      \"evidence\": \"ChIP, RNA-IP, minigene splicing assays and knockdown in the context of SPA lncRNA and PWS bodies\",\n      \"pmids\": [\"40147944\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of FUBP1 enrichment in PWS bodies unknown\", \"How transcriptional and splicing roles are coordinated unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"FUBP1 was implicated in miRNA strand-selective processing, supporting miR-155-3p maturation in macrophages.\",\n      \"evidence\": \"RNA-binding protein knockdown with strand-selective miRNA quantification\",\n      \"pmids\": [\"40825800\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Direct binding to pre-miR-155 not shown\", \"Mechanism of strand selection not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how FUBP1's distinct activities — FUSE-DNA transcriptional control, 3' splice-site stabilization, Nm/m6A RNA reading, and 5'UTR translational activation — are partitioned and coordinated within a single protein across subcellular compartments and cell states.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating DNA-binding and RNA-binding functions\", \"Determinants of nuclear versus cytoplasmic activity not defined\", \"Substrate/target selection rules across contexts unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 9, 10]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 2, 3, 5, 11]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [24, 12, 21, 7]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [19, 20, 1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [11, 19]},\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 5, 2, 3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [24, 7, 12, 21]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [12, 21, 13, 18]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"U2AF2\", \"SF1\", \"RUNX1\", \"EIF3\", \"TNPO1\", \"USP29\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":9,"faith_total":9,"faith_pct":100.0}}