Affinage

SUFU

Suppressor of fused homolog · UniProt Q9UMX1

Length
484 aa
Mass
53.9 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUFU is an essential negative regulator of Hedgehog (Hh) signaling and a tumor suppressor that controls the activity, stability, and subcellular distribution of GLI/Ci transcription factors (PMID:12068298, PMID:12426310). It binds GLI directly through a conserved SYGH motif (Gly122/His123 critical), and structural analysis of full-length human SUFU bound to the GLI SYGHL peptide shows that GLI engagement drives major conformational rearrangement including an intrinsically disordered loop required for pathway activation (PMID:12426310, PMID:24311597). SUFU engages Ci/GLI at two sites: an N-terminal SIN site that mediates cytoplasmic sequestration and a C-terminal SIC site that represses nuclear GLI by masking the CBP coactivator surface (PMID:25941387). As a nucleocytoplasmic shuttle, SUFU competes with importin β1 for the GLI1 N-terminus and recruits nuclear corepressors such as p66β (NuRD) onto Hh target promoters, and its balanced nucleo-cytoplasmic distribution is itself required for repressive function (PMID:24854174, PMID:25403183, PMID:24018050). SUFU also promotes formation of the GLI3 repressor by assembling a trimolecular GLI3/SUFU/GSK3β complex that licenses GLI3 phosphorylation and processing (PMID:19622347), and stabilizes full-length GLI by antagonizing the GLI-degrading factor SPOP (PMID:19684112). Hh stimulation recruits SUFU-GLI complexes to the primary cilium and triggers their dissociation, releasing GLI to the nucleus; PKA activity restrains ciliary localization, and dual phosphorylation of SUFU at Ser342 (GSK3β) and Ser346 (PKA) stabilizes SUFU until Hh-induced dephosphorylation drives retrograde export and proteasomal degradation (PMID:20956384, PMID:21317289). SUFU abundance is set by a network of ubiquitin ligases and kinases—degradative polyubiquitylation by Fbxl17 (nuclear) and LNX1, K63-linked non-proteolytic ubiquitylation by Itch/β-arrestin2 that enhances GLI3 repressor formation, and stabilizing phosphorylation by Nek2A—while GLI-SUFU affinity is weakened by ERK2 multisite phosphorylation of GLI1 (S102/S116/S130) and PRMT7 methylation of GLI2 (PMID:27234298, PMID:27297360, PMID:28035348, PMID:29515120, PMID:33608498, PMID:35831023, PMID:31000813). Beyond Hh, SUFU acts through additional mechanisms: cytoplasmic retention of ZNF281 to suppress tumor cell migration, activation of LATS1 to suppress the YAP/ACSL4 axis and modulate ferroptosis sensitivity, repression of WNT/β-catenin signaling, and direct binding to TRAF6 to block its phase separation, autoubiquitination, and NF-κB activation in innate immunity (PMID:36220888, PMID:35800779, PMID:15077159, PMID:37441604). Loss-of-function and hypomorphic SUFU variants cause disease: recessive missense variants that destabilize SUFU and impair GLI3 processing cause Joubert syndrome (PMID:28965847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 Medium

    Established SUFU as a tumor suppressor acting by controlling GLI nuclear-cytoplasmic localization, answering how SUFU restrains SHH signaling at the level of transcription factor compartmentalization.

    Evidence Patient-derived SUFU truncation mutants assayed for GLI nuclear export

    PMID:12068298

    Open questions at the time
    • Does not define the direct SUFU-GLI binding interface
    • Mechanism of export (shuttle vs. retention) not resolved
  2. 2002 High

    Mapped the direct physical SUFU-GLI interaction to a conserved SYGH motif, establishing the molecular basis of GLI recognition.

    Evidence Co-IP, Far Western, site-directed mutagenesis (Gly122/His123), luciferase reporter

    PMID:12426310

    Open questions at the time
    • Structural mechanism of binding not yet visualized
    • Whether a single binding mode accounts for both cytoplasmic and nuclear repression unknown
  3. 2004 Medium

    Defined SUFU as a nucleocytoplasmic shuttle protein with nuclear and cytoplasmic partners, and extended its repressive role to WNT/β-catenin signaling.

    Evidence Yeast two-hybrid (SAP18, Galectin3), NES mutant and leptomycin B; β-catenin/TCF reporter with medulloblastoma mutant

    PMID:14611647 PMID:15077159

    Open questions at the time
    • Physiological significance of SAP18/Galectin3 interactions in Hh unclear
    • Directness of SUFU-β-catenin binding not biochemically resolved
  4. 2009 High

    Showed SUFU promotes GLI3 repressor formation and controls full-length GLI levels, distinguishing its scaffolding (GSK3β recruitment) and stabilizing (SPOP antagonism) roles.

    Evidence Co-IP of GLI3/SUFU/GSK3β trimolecular complex, Sufu-/- MEFs, SPOP epistasis, cross-species rescue

    PMID:19622347 PMID:19684112

    Open questions at the time
    • Quantitative contribution of processing vs. stabilization to repression not separated
    • Cilium-dependence of these steps not fully delineated
  5. 2011 High

    Defined ciliary recruitment and phospho-regulated stability as the dynamic switch controlling SUFU release of GLI, answering how Hh stimulation reverses SUFU repression.

    Evidence Live imaging of endogenous SUFU-Gli at cilia, PKA perturbation; S342/S346 phosphosite mutagenesis and degradation assays

    PMID:20956384 PMID:21317289

    Open questions at the time
    • Identity of the Shh-triggered phosphatase not defined
    • Coupling between dephosphorylation and the degradation machinery unresolved
  6. 2012 High

    Genetically established Kif7 as the positive regulator that restricts SUFU by promoting its turnover and ciliary exclusion, with combined loss driving basal cell carcinoma.

    Evidence Kif7-null and compound mutant mouse genetics, ciliary localization, skin-specific double KO

    PMID:21795282 PMID:23034632

    Open questions at the time
    • Molecular mechanism by which Kif7 promotes SUFU turnover not defined
    • Tissue specificity of the SUFU-Kif7 balance not generalized
  7. 2014 High

    Resolved the structural and dual-site basis of SUFU-GLI binding and added nuclear corepressor recruitment and importin competition as parallel repressive mechanisms.

    Evidence X-ray crystallography and SAXS of SUFU-GLI; SIN/SIC site mutagenesis and CBP competition; importin β1 affinity and competition; p66β/Mycbp proteomics and ChIP

    PMID:24311597 PMID:24854174 PMID:25403183 PMID:25941387

    Open questions at the time
    • How the SIN/SIC sites are coordinated in vivo unclear
    • Dynamics of corepressor exchange at promoters not time-resolved
  8. 2018 High

    Defined an extensive ubiquitin/kinase network setting SUFU abundance and GLI-binding affinity, linking post-translational control to disease mutations.

    Evidence Fbxl17 (nuclear) and Itch/β-arrestin2 (K63) ubiquitylation assays, Nek2A kinase/ChIP feedback, K257 ubiquitin site, ERK2 and PRMT7 modification of GLI, LNX1/SNEP1 feedback

    PMID:18997815 PMID:27234298 PMID:27297360 PMID:28035348 PMID:29515120 PMID:31000813 PMID:33608498 PMID:35831023

    Open questions at the time
    • Hierarchy and crosstalk among the competing modifications unresolved
    • Spatial (nuclear vs. ciliary) compartmentalization of each ligase not fully mapped
  9. 2017 Medium

    Identified Hh-independent and tumor-relevant SUFU functions, broadening its role beyond GLI regulation.

    Evidence BCL-2 family BH-domain engagement of SUFU; ZNF281 cytoplasmic retention; LATS1/YAP/ACSL4 ferroptosis axis; dendritic cell HLA-DR/MLR regulation

    PMID:26067905 PMID:28945232 PMID:35800779 PMID:36220888

    Open questions at the time
    • Degree of GLI-independence varies and is not always cleanly separated
    • Physiological contexts for each non-canonical function not fully established
  10. 2017 Medium

    Connected SUFU loss-of-function to a Mendelian ciliopathy, showing hypomorphic variants impair GLI3 processing.

    Evidence Patient fibroblast functional studies of stability, GLI3 binding and cleavage; molecular dynamics

    PMID:28965847

    Open questions at the time
    • Genotype-phenotype correlation across variants not established
    • Tissue-specific consequences during development not defined
  11. 2023 High

    Revealed a direct innate immune function of SUFU through inhibition of TRAF6 phase separation and NF-κB activation, defining a Hh-independent role in inflammation.

    Evidence Reconstituted phase separation with purified proteins, FRAP, Native-PAGE, reciprocal Co-IP, myeloid-specific Sufu KO with LPS/CLP and TRAF6 rescue

    PMID:37441604

    Open questions at the time
    • Whether SUFU regulates other phase-separating signaling hubs unknown
    • Relationship between SUFU's Hh and TRAF6 pools not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing post-translational modifications, ciliary trafficking, and Hh-independent partners are integrated to set SUFU dosage in a given cell type remains unresolved.
  • No unified quantitative model of SUFU stability control across compartments
  • The Shh-induced phosphatase acting on SUFU is unidentified
  • Mechanistic basis for selecting Hh vs. non-canonical SUFU functions is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0140313 molecular sequestering activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005929 cilium 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
FBXL17GLI1GLI2GLI3GSK3BITCHTRAF6ZNF281
Complex memberships
GLI3/SUFU/GSK3β complexItch/β-arrestin2 complexSUFU-GLI complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SUFU mutations (including truncations) abolish its ability to export GLI transcription factors from nucleus to cytoplasm, resulting in activation of SHH signaling; SUFU functions as a tumor suppressor by modulating SHH signaling through nuclear-cytoplasmic regulation of GLI. Mutational analysis of patient-derived SUFU truncations with functional readout of GLI nuclear localization Nature genetics Medium 12068298
2002 SUFU directly interacts with GLI proteins via a conserved SYGH motif in GLI/Ci; residues Gly122 and His123 in this motif are critical for binding. A C-terminal 19-amino acid deletion in SUFU (Δ465) abolishes interaction with GLI1. GLI mutants lacking the SYGH motif are no longer suppressed by SUFU co-expression. Co-immunoprecipitation, Far Western assays, truncation and site-directed mutagenesis, luciferase reporter functional assay The Journal of biological chemistry High 12426310
2004 SUFU interacts with SAP18 (Sin3-associated polypeptide 18) and Galectin3 as nuclear binding partners. Co-expression with SAP18 translocates SUFU to the nucleus, while co-expression with SUFU translocates Galectin3 to the cytoplasm. SUFU is predominantly cytoplasmic but becomes mostly nuclear when its putative nuclear export signal is mutated or after leptomycin B treatment, establishing SUFU as a nucleocytoplasmic shuttle protein. Yeast two-hybrid screen, co-immunoprecipitation, cell transfection with NES mutant and leptomycin B treatment, subcellular fractionation/imaging The Biochemical journal Medium 14611647
2006 GSK3β binds to SUFU both in vitro and in vivo and phosphorylates SUFU; a phosphorylation-mimicking SUFU mutant shows significantly decreased ability to bind GLI1 and cannot suppress GLI-mediated reporter gene expression. GSK3β knockdown attenuates Hedgehog signaling, suggesting GSK3β functions as a positive regulator of Hedgehog signaling through phosphorylation of SUFU. Mass spectrometric identification of binding partner, GST pull-down and co-immunoprecipitation (in vitro and in vivo), in vitro kinase assay, RNAi knockdown, luciferase reporter assay Biochemical and biophysical research communications High 17182001
2008 Hedgehog signaling promotes ubiquitination of SUFU, leading to its proteasomal degradation. Lysine 257 (K257) is the ubiquitin attachment site; the K257R mutant of SUFU is more stable, more potent as a transcription repressor, and a stronger cell growth inhibitor. In vivo ubiquitination assay, site-directed mutagenesis (K257R), proteasome inhibitor experiments, transcription repressor and cell growth assays Oncogene High 18997815
2009 SUFU promotes Gli3 processing into its repressor form by recruiting GSK3β; SUFU can bind both GSK3β and Gli3 simultaneously, forming a trimolecular complex Gli3/SUFU/GSK3β that facilitates phosphorylation of Gli3 by GSK3β. Sonic Hh stimulation dissociates the SUFU/GSK3β complex from Gli3, blocking Gli3 processing. In SUFU-deficient MEFs, Gli3 processing is severely impaired. Co-immunoprecipitation, siRNA knockdown, Sufu−/− mouse embryonic fibroblasts with functional Gli3 processing readout Biochemical and biophysical research communications High 19622347
2009 SUFU controls protein levels of full-length Gli transcription factors (Gli activators and repressors) in a cilium-independent manner, partly by antagonizing the activity of Spop, a Gli-degrading factor. Zebrafish and fly Sufu can restore Gli protein function in Sufu-deficient mammalian cells, indicating evolutionary conservation of this mechanism. Sufu conditional knockout mice, cell-based reconstitution with heterologous Sufu orthologs, Spop epistasis analysis Genes & development High 19684112
2010 In vertebrates, Hedgehog stimulation rapidly recruits endogenous SUFU-Gli complexes to primary cilia, then causes rapid dissociation of SUFU-Gli complexes, allowing Gli to enter the nucleus and activate transcription. PKA activation blocks ciliary localization of SUFU-Gli complexes, preventing their Hh-induced dissociation. Live-cell imaging of endogenous SUFU-Gli complexes at cilia, pharmacological PKA activation/inhibition, colocalization and biochemical dissociation assays The Journal of cell biology High 20956384
2011 SUFU is phosphorylated at Ser-342 by GSK3β and at Ser-346 by PKA; dual phosphorylation at these sites stabilizes SUFU against Shh-induced degradation. Shh signaling induces trafficking of phospho-SUFU to the primary cilium in a complex with Gli2/3, and dephosphorylation triggers retrograde export and ubiquitin-proteasome degradation of SUFU. Site-directed mutagenesis (S342A, S346A, phosphomimetic S342D/S346D), PKA inhibitors, ciliary localization assays, ubiquitin-proteasome pathway analysis The Journal of biological chemistry High 21317289
2012 Kif7 promotes turnover of SUFU and exclusion of SUFU-Gli complexes from the primary cilium, thereby restricting SUFU's inhibitory function. Halving the dose of Sufu restores normal Hedgehog pathway activity and chondrocyte development in Kif7-null mice, establishing that Kif7's positive role in Hh signaling is to restrict SUFU activity. Kif7-null and compound mutant mouse genetics (epistasis), ciliary localization of SUFU-Gli complexes, SUFU protein level analysis Development (Cambridge, England) High 21795282
2012 Sufu restricts Gli2 activity through cytoplasmic sequestration in keratinocytes; Kif7 promotes Hh pathway activity by dissociating the SUFU-Gli2 complex. Simultaneous deletion of SUFU and Kif7 in adult epidermis induces basal cell carcinoma, whereas deletion of either alone cannot. Conditional knockout mice (skin-specific), genetic epistasis (single and double mutants), subcellular localization analysis Development (Cambridge, England) High 23034632
2013 Crystal structure and SAXS structure of full-length human SUFU and its complex with the conserved SYGHL motif of GLI reveal that GLI binding induces major conformational changes in SUFU, including rearrangement of an intrinsically disordered loop crucial for pathway activation. X-ray crystallography, small-angle X-ray scattering (SAXS), structural analysis of SUFU-GLI peptide complex Acta crystallographica. Section D, Biological crystallography High 24311597
2014 SUFU can bind Ci/Gli through two distinct sites: the N-terminal Sufu-interacting site (SIN) and a newly identified C-terminal Sufu-interacting site (SIC). Binding via SIN mediates cytoplasmic sequestration of Ci/Gli, while binding via SIC inhibits Ci/Gli activity in the nucleus by masking the CBP coactivator binding site in the C-terminal region of Ci. Binding site mutagenesis, cytoplasmic/nuclear localization assays, Drosophila genetics, CBP binding competition assay Proceedings of the National Academy of Sciences of the United States of America High 25941387
2014 Importin β1 and SUFU bind to overlapping sites on the GLI1 N-terminus with high nanomolar affinity; they compete for binding to GLI1, such that relative intracellular concentrations of SUFU and importin β1 determine GLI1 nuclear localization. SUFU co-expression specifically inhibits GFP-Gli1 nuclear accumulation. Quantitative live mammalian cell imaging, direct binding affinity measurement, siRNA knockdown of importin β1, competition binding assay The Biochemical journal High 24854174
2014 In the nucleus, SUFU recruits p66β (a NuRD repressor complex member) to block Gli-mediated Hh target gene expression; Mycbp forms a complex with Gli and SUFU without Hh stimulation but is kept inactive. Hh activation leads to dissociation of SUFU/p66β from Gli, enabling Mycbp to promote Gli activity. SUFU, p66β, Mycbp, and Gli are detected on promoters of Hh targets in a dynamic manner. Proteomic identification of Sufu-interacting proteins, cell-based signaling assays, zebrafish epistasis, chromatin immunoprecipitation (ChIP) Genes & development High 25403183
2016 The F-box protein Fbxl17 targets SUFU for proteolysis specifically in the nucleus, mediating its polyubiquitylation and allowing Gli1 release for Hh signal transduction. Depletion of Fbxl17 leads to defective Hh signaling and impaired medulloblastoma tumor growth. A Gorlin syndrome-derived SUFU mutation increases SUFU turnover through enhanced Fbxl17-mediated polyubiquitylation. Co-immunoprecipitation, ubiquitylation assay, nuclear-targeted constructs, Fbxl17 depletion in cells and tumor models, patient-derived mutation analysis The EMBO journal High 27234298
2016 Nek2A binds SUFU (identified by yeast two-hybrid, GST pull-down and co-immunoprecipitation), phosphorylates SUFU, and stabilizes it against ubiquitin/proteasome degradation. Phosphorylated SUFU inhibits nuclear localization and transcriptional activity of Gli2. In turn, Gli1 and Gli2 directly bind the NEK2A gene promoter to induce its transcription, forming a negative-feedback loop. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, in vitro kinase assay, chromatin immunoprecipitation (ChIP), reporter assay Cellular signalling / International journal of oncology Medium 27297360 28035348
2017 BCL-2 family anti-apoptotic proteins (MCL-1, BCL-2, BCL-XL) found outside the outer mitochondrial membrane engage a BH domain sequence in SUFU, directly promote SUFU turnover, inhibit SUFU-GLI interaction, and thereby induce expression of GLI target genes including BCL-2, MCL-1, and BCL-XL (feedforward loop). BH3 mimetics can disable this interaction. Co-immunoprecipitation, SUFU-GLI interaction assays, SUFU stability assays, BH3 mimetic pharmacological disruption, GLI target gene expression Nature cell biology High 28945232
2018 The Itch/β-arrestin2 complex binds SUFU and induces its Lys63-linked (non-proteolytic) polyubiquitylation, which increases SUFU association with Gli3 and promotes conversion of Gli3 into its repressor form, keeping Hh signaling off. Hh activation antagonizes Itch-dependent polyubiquitylation of SUFU. SUFU mutations found in medulloblastoma patients are insensitive to Itch activity. Co-immunoprecipitation, ubiquitylation assays (K63-specific), Gli3 processing assays, patient-derived mutation analysis, Hh pathway activation/inhibition Nature communications High 29515120
2019 PRMT7 methylates GLI2 at arginine residues R225 and R227, which are located near the SUFU-binding region. This methylation interferes with GLI2-SUFU binding, leading to increased GLI2 nuclear accumulation and enhanced Shh signaling. PRMT7-deficient MEFs show increased GLI2-SUFU interaction and reduced Shh signaling. Co-immunoprecipitation, in vitro methylation assay, site-directed mutagenesis (R225/R227), GLI2 nuclear localization assay, PRMT7 KO MEFs Cell death and differentiation High 31000813
2021 SNEP1, a Hh transcriptional target, enhances SUFU ubiquitination and proteasomal degradation by recruiting the E3 ubiquitin ligase LNX1, thereby promoting Hh signaling in a positive feedback manner. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor experiments, LNX1 knockdown, Hh reporter assay Cell death & disease Medium 33608498
2022 SUFU suppresses ferroptosis sensitivity in breast cancer cells by activating LATS1 to suppress YAP, thereby reducing ACSL4 expression. Deletion of SUFU residues 174-385 disrupts SUFU binding to LATS1, abolishing its regulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Co-immunoprecipitation, SUFU deletion mutant mapping (residues 174-385), ACSL4 expression analysis, RSL3-triggered ferroptosis assay, ectopic expression and depletion iScience Medium 35800779
2022 ERK2 phosphorylates GLI1 at three evolutionarily conserved sites (S102, S116, S130) near the high-affinity SUFU-binding site; multisite phosphorylation cooperates to weaken GLI1-SUFU binding by over 25-fold. Phosphomimetic substitutions at all three sites enhance GLI1 transcriptional activity in cells. Single or pairwise phosphorylations do not achieve the same level of SUFU release. In vitro ERK2 kinase assay, site-directed mutagenesis (phosphomimetic and phospho-dead substitutions), quantitative binding affinity measurement, transcriptional reporter assay Life science alliance High 35831023
2022 SUFU binds the transcription factor ZNF281 (a mammalian-specific protein with no Drosophila homolog) and retains it in the cytoplasm by masking ZNF281's nuclear localization signal; SUFU also hampers ZNF281 interaction with target gene promoters, suppressing tumor cell migration independent of the canonical Hh pathway. Co-immunoprecipitation, subcellular localization assays, ChIP/promoter-binding assays, in vivo tumor migration model, NLS masking mutant analysis Cell death and differentiation Medium 36220888
2023 SUFU directly interacts with TRAF6 and prevents TRAF6 oligomerization, phase separation (liquid-liquid phase separation into droplets), and autoubiquitination. SUFU inhibits NF-κB activation upon LPS stimulation by suppressing TRAF6 phase-separated droplet formation. In myeloid cell-specific Sufu-KO mice, LPS-induced inflammation and lethality are aggravated and rescued by TRAF6 depletion. Co-immunoprecipitation, in vitro phase separation assay with purified proteins, FRAP, Native-PAGE, myeloid cell-specific KO mice with LPS-induced septic shock and CLP models Theranostics High 37441604
2015 SUFU depletion in recipient dendritic cells leads to increased surface HLA-DR expression and augmented allogeneic mixed leukocyte response, while ectopic SUFU expression reduces HLA-DR and suppresses MLR, demonstrating a role for SUFU in regulating dendritic cell antigen presentation. Ectopic expression and siRNA knockdown of SUFU in THP-1-derived DCs, HLA-DR surface expression measurement, allogeneic mixed leukocyte response assay Scientific reports Medium 26067905
2004 A medulloblastoma-derived mutant of SUFU loses the ability to decrease nuclear levels of β-catenin and cannot inhibit β-catenin/TCF-mediated transcription, indicating that wild-type SUFU can bind β-catenin, export it from the nucleus, and repress WNT signaling. Nuclear β-catenin localization assay, β-catenin/TCF luciferase reporter assay with wild-type vs. mutant SUFU Oncogene Medium 15077159
2006 Drosophila Su(fu) enters the nucleus in concert with Ci in response to Hh signaling; Ci can bring Su(fu) with it to a multimerized Ci DNA-binding site, and Su(fu) nuclear import depends on the Ci nuclear localization signal. Cell biological localization assay, NLS mutant analysis, multimerized DNA binding site tethering assay Developmental biology Medium 16595130
2017 Recessive hypomorphic missense variants in SUFU reduce SUFU protein stability and its capacity to bind GLI3 and promote GLI3 cleavage into the repressor form GLI3R, impairing SUFU-mediated repression of the SHH pathway and causing Joubert syndrome. Molecular dynamics simulation, functional studies in cellular models and patient fibroblasts (SUFU stability, GLI3 binding, GLI3 cleavage, Hh target gene expression) American journal of human genetics Medium 28965847
2013 RIO kinase 3 (RIOK3) modulates SUFU subcellular distribution; a SUFU construct experimentally tethered exclusively to the nucleus is unable to antagonize endogenous Hh signaling (negative finding: nuclear-only SUFU loses inhibitory function), indicating that normal nucleo-cytoplasmic distribution of SUFU is required for its negative regulatory role. Kinase screen in human cells, nuclear-tethered SUFU construct functional assay, RIOK3 overexpression and SUFU localization analysis Cellular signalling Medium 24018050

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in SUFU predispose to medulloblastoma. Nature genetics 608 12068298
2007 MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proceedings of the National Academy of Sciences of the United States of America 450 18077375
2010 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. The Journal of cell biology 319 20956384
2005 Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. The British journal of dermatology 313 15656799
2009 Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes & development 300 19684112
2014 Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 214 25403219
2006 Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. The Journal of pathology 188 16294371
2002 Characterization of the physical interaction of Gli proteins with SUFU proteins. The Journal of biological chemistry 147 12426310
2009 Identification of a SUFU germline mutation in a family with Gorlin syndrome. American journal of medical genetics. Part A 139 19533801
2018 Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Molecular carcinogenesis 126 29749061
2012 Loss of SUFU function in familial multiple meningioma. American journal of human genetics 123 22958902
2019 lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling. Journal of cellular biochemistry 98 31692053
2012 The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia. Human molecular genetics 94 23026747
2004 The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins. The Biochemical journal 93 14611647
2011 Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium. The Journal of biological chemistry 92 21317289
2012 High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 91 22508808
2010 SufU is an essential iron-sulfur cluster scaffold protein in Bacillus subtilis. Journal of bacteriology 82 20097860
2009 Sufu recruits GSK3beta for efficient processing of Gli3. Biochemical and biophysical research communications 81 19622347
2018 MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression. Cell death & disease 80 29915227
2008 Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene 69 18997815
2016 MiRNA-194 activates the Wnt/β-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator, SUFU. Cancer letters 67 27810403
2021 Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu). Stem cell research & therapy 65 34099038
2013 Fe-S cluster biogenesis in Gram-positive bacteria: SufU is a zinc-dependent sulfur transfer protein. Biochemistry 65 24321018
2015 Multisite interaction with Sufu regulates Ci/Gli activity through distinct mechanisms in Hh signal transduction. Proceedings of the National Academy of Sciences of the United States of America 63 25941387
2012 Kif7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis. Development (Cambridge, England) 62 23034632
2004 Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. Oncogene 62 15077159
2016 SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development. The EMBO journal 57 27234298
2013 Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta crystallographica. Section D, Biological crystallography 57 24311597
2012 Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation. Familial cancer 57 22829011
2011 Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma. Familial cancer 54 21188540
2019 Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu. Stem cell research & therapy 53 30898155
2018 Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis. Nature communications 52 29515120
2017 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects. American journal of human genetics 48 28965847
2016 Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation. JAMA dermatology 48 26677003
2006 GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells. Biochemical and biophysical research communications 48 17182001
2022 SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway. iScience 47 35800779
2011 Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development (Cambridge, England) 47 21795282
2015 microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu). Oncotarget 46 26462018
2009 Structural studies of the Enterococcus faecalis SufU [Fe-S] cluster protein. BMC biochemistry 46 19187533
2008 Role and regulation of human tumor suppressor SUFU in Hedgehog signaling. Advances in cancer research 46 19055941
2021 Periodontitis-compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling. Cell proliferation 44 33759282
2009 Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. Journal of medical genetics 43 19833601
2017 Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. Nature cell biology 41 28945232
2014 Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling. Genes & development 39 25403183
2016 Crosstalk between the vitamin D receptor (VDR) and miR-214 in regulating SuFu, a hedgehog pathway inhibitor in breast cancer cells. Experimental cell research 36 27693451
2019 Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals. Nature communications 35 31604927
2017 Zinc-Ligand Swapping Mediated Complex Formation and Sulfur Transfer between SufS and SufU for Iron-Sulfur Cluster Biogenesis in Bacillus subtilis. Journal of the American Chemical Society 35 29235855
2006 Regulation of Ci and Su(fu) nuclear import in Drosophila. Developmental biology 34 16595130
2019 LIFR-AS1 modulates Sufu to inhibit cell proliferation and migration by miR-197-3p in breast cancer. Bioscience reports 33 31127025
2019 GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis. Cell reports 32 31167144
2011 Volatile components of the enzyme-ripened sufu, a Chinese traditional fermented product of soy bean. Journal of bioscience and bioengineering 30 22051578
2023 Sufu limits sepsis-induced lung inflammation via regulating phase separation of TRAF6. Theranostics 29 37441604
2021 SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. Journal of medical genetics 28 34675124
2011 Mechanistic characterization of sulfur transfer from cysteine desulfurase SufS to the iron-sulfur scaffold SufU in Bacillus subtilis. FEBS letters 28 21236255
2018 Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same. Familial cancer 27 29356994
2023 Structural and Biochemical Characterization of Mycobacterium tuberculosis Zinc SufU-SufS Complex. Biomolecules 26 37238602
2021 Metagenomic insights into the bacteria responsible for producing biogenic amines in sufu. Food microbiology 25 33875200
2019 PRMT7 methylates and suppresses GLI2 binding to SUFU thereby promoting its activation. Cell death and differentiation 25 31000813
2016 Crystal Structure of Bacillus subtilis Cysteine Desulfurase SufS and Its Dynamic Interaction with Frataxin and Scaffold Protein SufU. PloS one 24 27382962
2011 Enterococcus faecalis SufU scaffold protein enhances SufS desulfurase activity by acquiring sulfur from its cysteine-153. Biochimica et biophysica acta 23 21835272
2010 Some biochemical and physical changes during the preparation of the enzyme-ripening sufu, a fermented product of soybean curd. Journal of agricultural and food chemistry 22 20218723
2021 Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer. Aging 21 33848981
2019 Mesenchymal Sufu Regulates Development of Mandibular Molars via Shh Signaling. Journal of dental research 21 31499014
2018 Effective anti-programmed death-1 therapy in a SUFU-mutated patient with Gorlin-Goltz syndrome. The British journal of dermatology 21 29603722
2017 miR-342-3p elevates osteogenic differentiation of umbilical cord mesenchymal stem cells via inhibiting Sufu in vitro. Biochemical and biophysical research communications 21 28765042
2020 High-Throughput Sequencing and Metabolomics Reveal Differences in Bacterial Diversity and Metabolites Between Red and White Sufu. Frontiers in microbiology 20 32390991
2017 Reduction of biogenic amines in sufu by ethanol addition during ripening stage. Food chemistry 20 28873546
2014 Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development. Developmental biology 20 24886827
2021 Positive feedback of SuFu negating protein 1 on Hedgehog signaling promotes colorectal tumor growth. Cell death & disease 19 33608498
2014 Overlapping binding sites for importin β1 and suppressor of fused (SuFu) on glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization. The Biochemical journal 19 24854174
2021 MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT. Heliyon 18 33912703
2018 miR-423-5p inhibits myoblast proliferation and differentiation by targeting Sufu. Journal of cellular biochemistry 18 29923621
2018 MicroRNA-874 targeting SUFU involves in osteoblast proliferation and differentiation in osteoporosis rats through the Hedgehog signaling pathway. Biochemical and biophysical research communications 18 30342851
2016 Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway. International journal of oncology 18 28035348
2025 Effects of Cold Post-Fermentation Process on Microbial Diversity and Biogenic Amines in Protease-Assisted Fermented sufu. Foods (Basel, Switzerland) 17 40077437
2022 ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1. Life science alliance 17 35831023
2020 Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia. Genetics in medicine : official journal of the American College of Medical Genetics 17 33024317
2012 Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular Gli activities in Hedgehog signaling. PloS one 17 23166838
2004 No evidence for mutations or altered expression of the Suppressor of Fused gene (SUFU) in primitive neuroectodermal tumours. Neuropathology and applied neurobiology 17 15488029
2000 Genomic organization, chromosomal assignment, and expression analysis of the mouse suppressor of fused gene (Sufu) coding a Gli protein partner. Mammalian genome : official journal of the International Mammalian Genome Society 17 10920228
2020 miR-214-3p-Sufu-GLI1 is a novel regulatory axis controlling inflammatory smooth muscle cell differentiation from stem cells and neointimal hyperplasia. Stem cell research & therapy 16 33143723
2017 Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. International journal of molecular sciences 16 28640224
2016 Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism. Cellular signalling 16 27297360
2015 Multiple skin hamartomata: a possible novel clinical presentation of SUFU neoplasia syndrome. Familial cancer 16 25287320
2013 RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling. Cellular signalling 16 24018050
2011 Fermentation temperature affects the antioxidant activity of the enzyme-ripened sufu, an oriental traditional fermented product of soybean. Journal of bioscience and bioengineering 16 21497549
2004 Mucoraceous moulds involved in the commercial fermentation of Sufu Pehtze. Antonie van Leeuwenhoek 16 15028872
2022 Inhibition of the transcription factor ZNF281 by SUFU to suppress tumor cell migration. Cell death and differentiation 15 36220888
2022 Sufu- and Spop-mediated regulation of Gli2 is essential for the control of mammalian cochlear hair cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 15 36252002
2021 Microbial Community Succession and Metabolite Changes During Fermentation of BS Sufu, the Fermented Black Soybean Curd by Rhizopus microsporus, Rhizopus oryzae, and Actinomucor elegans. Frontiers in microbiology 15 34248874
2015 Sufu and Kif7 in limb patterning and development. Developmental dynamics : an official publication of the American Association of Anatomists 15 25581370
2020 SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer. Cell cycle (Georgetown, Tex.) 14 33017570
2012 Suppressor of fused (Sufu) mediates the effect of parathyroid hormone-like hormone (Pthlh) on chondrocyte differentiation in the growth plate. The Journal of biological chemistry 14 22930757
2021 Comparative analysis of the microbial community and nutritional quality of sufu. Food science & nutrition 13 34401063
2019 Effects of miRNA-342-3p in modulating Hedgehog signaling pathway of human umbilical cord mesenchymal stem cells by down-regulating Sufu. Oral diseases 13 30790389
2018 Itraconazole perturbs colorectal cancer dormancy through SUFU-mediated WNT inhibition. Molecular & cellular oncology 13 30250932
2015 A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response. PloS one 13 26271100
2022 Dynamic correlations between major enzymatic activities, physicochemical properties and targeted volatile compounds in naturally fermented plain sufu during production. Food chemistry 12 35078100
2017 Down-regulation of microRNA-224 -inhibites growth and epithelial-to-mesenchymal transition phenotype -via modulating SUFU expression in bladder cancer cells. International journal of biological macromolecules 12 28780419
2015 Genome-wide single-nucleotide polymorphism analysis revealed SUFU suppression of acute graft-versus-host disease through downregulation of HLA-DR expression in recipient dendritic cells. Scientific reports 12 26067905

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