{"gene":"RPLP1","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":2017,"finding":"RPLP1 and RPLP2 form the ribosomal stalk by binding to RPLP0, and are specifically required for flavivirus (DENV, YFV, ZIKV) translation; knockdown strongly reduced early viral protein accumulation and reduced DENV structural proteins expressed from an exogenous transgene, implicating RPLP1/2 in translation elongation through the viral open reading frame.","method":"RNA interference knockdown, metabolic labeling of global protein synthesis, exogenous transgene expression assay, in two human cell lines (A549, HuH-7) and Aedes aegypti mosquitoes","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — validated in multiple cell lines and in vivo mosquito model with multiple orthogonal methods (RNAi, metabolic labeling, transgene reporter), replicated across biological contexts","pmids":["27974556"],"is_preprint":false},{"year":2020,"finding":"RPLP1 and RPLP2 relieve ribosome pausing within sequences encoding multiple adjacent transmembrane domains (TMDs); ribosome profiling in RPLP1/2-depleted cells showed ribosome pausing immediately downstream of sequences encoding two adjacent TMDs in the DENV envelope protein, and RPLP1/2 depletion disproportionately affected ribosome density on cellular mRNAs encoding multiple TMDs, implicating RPLP1/2 in co-translational folding and biogenesis of multi-pass transmembrane proteins.","method":"Ribosome profiling in RPLP1/2-depleted cells, siRNA knockdown, viral and cellular mRNA translation analysis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — ribosome profiling with genome-wide resolution, mechanistic follow-up on both viral and cellular substrates, multiple orthogonal analyses in a single rigorous study","pmids":["32890404"],"is_preprint":false},{"year":2024,"finding":"RPLP1 inhibits transcription of clade B HIV-1 by occupying C/EBPβ binding sites in the viral long terminal repeat (LTR); this interaction requires α-helices 2 and 4 of RPLP1; HIV-1 infection induces translocation of RPLP1 from the cytoplasm to the nucleus, which is essential for its antiviral activity; RPLP1 knockdown promotes reactivation of latent HIV-1 proviruses.","method":"Chromatin binding assays, domain mutagenesis (α-helix deletion), subcellular fractionation/confocal imaging for nuclear translocation, shRNA knockdown with latency reactivation assay, LTR reporter assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods including domain mutagenesis, localization studies, reporter assays, and latency reactivation in a single rigorous study","pmids":["38906865"],"is_preprint":false},{"year":2014,"finding":"Rplp1 is essential for embryonic nervous system development; conditional knockout in the CNS (Rplp1CNSΔ) caused perinatal lethality, brain atrophy, progenitor cell proliferation arrest and apoptosis with dysregulation of cyclin A, cyclin E, p21CIP1, p27KIP1, and p53; Rplp1 deletion in primary mouse embryonic fibroblasts (pMEFs) did not alter global protein synthesis but changed expression patterns of specific protein subsets involved in protein folding, unfolded protein response, cell death, and signal transduction, demonstrating translational 'fine-tuning'.","method":"Germline and conditional CNS knockout mouse, immunohistochemistry, western blot, 2D-DIGE proteomics of pMEFs, cell cycle and apoptosis analysis","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo genetic knockout combined with multiple orthogonal cellular and proteomic readouts establishing functional mechanism","pmids":["24959908"],"is_preprint":false},{"year":2009,"finding":"Overexpression of Rplp1 bypasses replicative senescence in primary mouse embryonic fibroblasts, producing a two-fold increase in E2F1 promoter activity and upregulation of cyclin E; co-expression with mutant RasVal12 contributes to transformation in NIH3T3 cells; p53 dominant-negative mutant (p53R175H) upregulates Rplp1, suggesting p53 mutation facilitates immortalization via Rplp1.","method":"ES cell cDNA library screen, retroviral overexpression in MEFs, E2F1 promoter luciferase assay, western blot for cyclin E, soft-agar colony formation assay with RasVal12 co-expression","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays (promoter reporter, transformation assay, Western blot) in a single lab with clear mechanistic readouts","pmids":["19233166"],"is_preprint":false},{"year":2024,"finding":"The transcription factor ESRRA (estrogen-related receptor alpha) transcriptionally activates the Rplp1 gene promoter; decreased ESRRA binding to the Rplp1 promoter during lipotoxicity reduces Rplp1 expression, which in turn reduces global protein translation and specifically impairs translation of lysosome proteins (Lamp2, Ctsd) and autophagy proteins (sqstm1, Map1lc3b); ESRRA does not directly increase binding to lysosome/autophagy gene promoters, confirming its regulation is at the translational level via Rplp1.","method":"Chromatin immunoprecipitation (ChIP) for ESRRA at Rplp1 promoter, siRNA/overexpression of Esrra and Rplp1, puromycin labeling of global translation, polysome profiling, proteomics in human primary hepatocytes, mouse AML12 cells, and in vivo mouse MASH model","journal":"Molecular metabolism","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — ChIP, polysome profiling, and proteomics with in vitro and in vivo validation across multiple model systems, orthogonal mechanistic approaches","pmids":["39032642"],"is_preprint":false},{"year":2025,"finding":"During prolonged starvation, ESRRA increases and transcriptionally stimulates Rplp1 gene expression to drive selective adaptive translation of lysosome and autolysosome proteins, thereby activating autophagy; Esrra overexpression or siRNA knockdown caused parallel changes in Rplp1 expression, lysosome/autophagy protein translation, and autophagy activity in vitro and in vivo.","method":"siRNA knockdown and overexpression of Esrra in vitro and in vivo, proteomic analysis, polysome profiling, mRNA transcription analysis, autophagy flux assays","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (proteomics, polysome profiling, transcriptomics, autophagy assays) replicated in vitro and in vivo in liver-specific Esrra knockout mice","pmids":["39936615"],"is_preprint":false},{"year":2022,"finding":"RPLP1 physically interacts with CSFV (classical swine fever virus) NS4B protein, as confirmed by co-immunoprecipitation, GST pulldown, and confocal co-localization; RPLP1 knockdown reduced viral protein expression and progeny virus titers without affecting CSFV IRES activity or intracellular viral RNA abundance, indicating RPLP1 promotes CSFV genome translation post-entry.","method":"Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, confocal microscopy, lentiviral shRNA knockdown, overexpression, dual-luciferase IRES reporter assay, viral titer measurement","journal":"Virulence","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding validated by three methods (Co-IP, GST pulldown, confocal), functional consequences assessed by multiple assays in a single lab","pmids":["35129423"],"is_preprint":false},{"year":2020,"finding":"RPLP1 is essential for endometriotic epithelial cell survival in vitro; stable shRNA knockdown of RPLP1 in an endometriosis cell line resulted in a significant decrease in cell survival.","method":"shRNA stable knockdown, cell survival assay, immunohistochemistry, western blotting, qRT-PCR in tissue specimens and cell lines","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotype, corroborated by tissue expression data, single lab","pmids":["31899515"],"is_preprint":false},{"year":2023,"finding":"RPLP1 knockdown in endometrial adenocarcinoma cell lines reduced cell survival and migration, establishing a role for RPLP1 in mediating these processes in endometrial cancer cells.","method":"siRNA knockdown in multiple endometrial adenocarcinoma cell lines (Ishikawa, HEC1A, HEC1B, AN3), cell survival and migration assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype in multiple cell lines, single lab","pmids":["36769010"],"is_preprint":false},{"year":2020,"finding":"CNN3 promotes the viability and motility of cervical cancer cells partly through downstream regulation of RPLP1 mRNA expression; rescue experiments showed that RPLP1 overexpression reversed phenotypes inhibited by CNN3 silencing, placing RPLP1 downstream of CNN3 in this pathway.","method":"RNA sequencing to identify downstream genes, siRNA knockdown of CNN3, RPLP1 overexpression rescue experiments, proliferation/migration/invasion assays, xenograft model","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established by rescue experiment, multiple functional assays and in vivo validation, single lab","pmids":["32051425"],"is_preprint":false},{"year":2007,"finding":"Giant panda RPLP1 protein contains three casein kinase II phosphorylation sites and two N-myristoylation sites, as predicted by topology analysis; the recombinant His-tagged RPLP1 protein was expressed in E. coli as an ~18 kDa polypeptide consistent with predictions.","method":"RT-PCR cloning, sequence alignment, topology/modification site prediction, recombinant expression in E. coli","journal":"International journal of biological sciences","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction of modification sites with no experimental validation of phosphorylation or myristoylation","pmids":["18071584"],"is_preprint":false}],"current_model":"RPLP1 is a component of the ribosomal stalk (formed with RPLP0 and RPLP2) that functions primarily to relieve ribosome pausing at sequences encoding multiple transmembrane domains, thereby promoting translation elongation and co-translational folding of multi-pass transmembrane proteins; it is transcriptionally induced by ESRRA to drive selective adaptive translation of lysosomal and autophagy proteins during starvation; it can translocate from cytoplasm to nucleus to restrict HIV-1 transcription by occupying C/EBPβ binding sites in the viral LTR; and it is required for efficient translation of flaviviral and other viral genomes, while also promoting cell survival and migration in multiple cancer contexts."},"narrative":{"mechanistic_narrative":"RPLP1 is a component of the ribosomal stalk that, together with RPLP2, assembles onto RPLP0 to regulate translation elongation, with a specialized role in relieving ribosome pausing within sequences encoding multiple adjacent transmembrane domains, thereby supporting co-translational folding and biogenesis of multi-pass transmembrane proteins [PMID:27974556, PMID:32890404]. Rather than governing bulk protein synthesis, RPLP1 acts as a translational 'fine-tuner': its loss in primary fibroblasts leaves global translation unchanged but reshapes the expression of defined protein subsets, and its deletion in the developing CNS causes progenitor proliferation arrest, apoptosis, and dysregulation of cell-cycle regulators, establishing an essential role in nervous system development [PMID:24959908]. This selective translational function is harnessed for metabolic adaptation: the transcription factor ESRRA binds and activates the Rplp1 promoter, and ESRRA-driven RPLP1 expression selectively promotes translation of lysosomal and autophagy proteins to activate autophagy during starvation and lipotoxic stress [PMID:39032642, PMID:39936615]. RPLP1 is also exploited by diverse viruses, being required for the elongation phase of flaviviral and classical swine fever virus genome translation through interactions with viral proteins, while a separate nuclear pool restricts HIV-1 by occupying C/EBPβ binding sites in the viral LTR [PMID:27974556, PMID:32890404, PMID:38906865, PMID:35129423]. Across several cancer contexts, RPLP1 promotes cell survival and migration [PMID:36769010, PMID:32051425].","teleology":[{"year":2009,"claim":"Established a pro-proliferative, immortalizing activity for RPLP1 distinct from a passive structural role, linking it to cell-cycle control.","evidence":"Retroviral overexpression in MEFs with E2F1 promoter reporter, cyclin E western blot, and Ras co-transformation/soft-agar assays","pmids":["19233166"],"confidence":"Medium","gaps":["Does not establish whether the effect is mediated through ribosomal/translational function or an extra-ribosomal activity","Mechanistic link to E2F1/cyclin E is correlative","Single-lab overexpression system"]},{"year":2014,"claim":"Showed RPLP1 is required for development and acts by translational fine-tuning of specific protein subsets rather than bulk synthesis, answering whether stalk loss equals global translation failure.","evidence":"Germline and conditional CNS knockout mice with immunohistochemistry, and 2D-DIGE proteomics of knockout pMEFs","pmids":["24959908"],"confidence":"High","gaps":["Identity of the direct mRNA targets selectively affected was not defined","Mechanism connecting stalk function to cell-cycle regulator dysregulation unresolved"]},{"year":2017,"claim":"Defined RPLP1 as a stalk subunit (with RPLP2 on RPLP0) specifically required for flavivirus genome translation, framing it as an elongation-phase factor.","evidence":"RNAi knockdown with metabolic labeling and transgene reporter assays in A549/HuH-7 cells and Aedes aegypti mosquitoes","pmids":["27974556"],"confidence":"High","gaps":["Did not yet define why viral ORFs are selectively dependent on RPLP1/2","No structural detail of stalk assembly in this context"]},{"year":2020,"claim":"Identified the molecular basis of RPLP1/2 selectivity: relief of ribosome pausing at sequences encoding adjacent transmembrane domains, explaining its preferential effect on multi-pass membrane proteins and viral structural proteins.","evidence":"Ribosome profiling in RPLP1/2-depleted cells with analysis of viral and cellular TMD-encoding mRNAs","pmids":["32890404"],"confidence":"High","gaps":["Structural mechanism by which the stalk resolves TMD-associated pausing not determined","Whether co-translational folding machinery is directly engaged not shown"]},{"year":2020,"claim":"Extended RPLP1's survival function to disease tissue, showing it is required for endometriotic epithelial cell survival.","evidence":"Stable shRNA knockdown with cell survival assays plus tissue expression analysis","pmids":["31899515"],"confidence":"Medium","gaps":["Molecular pathway linking RPLP1 to survival not defined","Single cell-line phenotype"]},{"year":2020,"claim":"Placed RPLP1 downstream of CNN3 in a cervical cancer proliferation/migration pathway via epistasis.","evidence":"RNA-seq identification, CNN3 knockdown with RPLP1 overexpression rescue, functional assays and xenograft","pmids":["32051425"],"confidence":"Medium","gaps":["How CNN3 regulates RPLP1 mRNA is unknown","Whether RPLP1's effect requires its ribosomal function not addressed"]},{"year":2022,"claim":"Demonstrated a direct physical interaction between RPLP1 and a viral protein (CSFV NS4B) and that RPLP1 supports viral genome translation post-entry independent of IRES activity.","evidence":"Yeast two-hybrid, Co-IP, GST pulldown, confocal co-localization, shRNA knockdown, dual-luciferase IRES reporter, and viral titer measurement","pmids":["35129423"],"confidence":"Medium","gaps":["Functional significance of the NS4B interaction for translation is not mechanistically resolved","Single-lab finding"]},{"year":2023,"claim":"Generalized RPLP1's pro-tumor role, showing it mediates survival and migration across multiple endometrial cancer cell lines.","evidence":"siRNA knockdown in four endometrial adenocarcinoma lines with survival and migration assays","pmids":["36769010"],"confidence":"Medium","gaps":["Downstream effectors not identified","Does not distinguish ribosomal from non-ribosomal mechanism"]},{"year":2024,"claim":"Identified ESRRA as a transcriptional driver of Rplp1 and showed this axis selectively controls translation of lysosomal and autophagy proteins, linking RPLP1 to metabolic stress responses.","evidence":"ChIP for ESRRA at the Rplp1 promoter, Esrra/Rplp1 perturbation, puromycin labeling, polysome profiling, and proteomics across hepatocytes, AML12 cells, and a mouse MASH model","pmids":["39032642"],"confidence":"High","gaps":["mRNA features that confer selective RPLP1 dependence of lysosome/autophagy transcripts not defined","Relationship to the TMD-pausing mechanism not addressed"]},{"year":2024,"claim":"Revealed a non-canonical nuclear function: HIV-1-induced cytoplasm-to-nucleus translocation of RPLP1 represses viral transcription by occupying C/EBPβ sites in the LTR, and its loss reactivates latent provirus.","evidence":"Chromatin binding assays, α-helix deletion mutagenesis, subcellular fractionation/confocal imaging, LTR reporter assays, and shRNA knockdown with latency reactivation","pmids":["38906865"],"confidence":"High","gaps":["Trigger and machinery for nuclear translocation not defined","How a stalk protein acquires sequence-specific DNA occupancy at C/EBPβ sites is unresolved"]},{"year":2025,"claim":"Consolidated the ESRRA-RPLP1 axis as a starvation-responsive program that drives selective adaptive translation of lysosome/autolysosome proteins to activate autophagy.","evidence":"Esrra perturbation in vitro and in vivo (liver-specific Esrra knockout mice), proteomics, polysome profiling, transcriptomics, and autophagy flux assays","pmids":["39936615"],"confidence":"High","gaps":["Direct demonstration that RPLP1 stalk activity (not abundance alone) confers selectivity is incomplete","Connection to membrane-protein biogenesis mechanism not integrated"]},{"year":null,"claim":"It remains unknown how a single ribosomal stalk subunit reconciles its distinct activities — relief of TMD ribosome pausing, selective translation of lysosome/autophagy proteins, viral genome translation, and sequence-specific nuclear transcriptional repression — and what structural features or post-translational signals partition RPLP1 between these roles.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model linking stalk function to substrate selectivity","Signals controlling cytoplasm-to-nucleus partitioning undefined","Predicted phosphorylation/myristoylation sites lack experimental validation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[1,3]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5,6]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,2,7]}],"complexes":["ribosomal stalk"],"partners":["RPLP0","RPLP2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P05386","full_name":"Large ribosomal subunit protein P1","aliases":["60S acidic ribosomal protein P1"],"length_aa":114,"mass_kda":11.5,"function":"Plays an important role in the elongation step of protein synthesis","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/P05386/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPLP1","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPRIN1","stoichiometry":10.0},{"gene":"EIF2S3","stoichiometry":10.0},{"gene":"ENY2","stoichiometry":10.0},{"gene":"G3BP1","stoichiometry":10.0},{"gene":"G3BP2","stoichiometry":10.0},{"gene":"NPM1","stoichiometry":10.0},{"gene":"RACK1","stoichiometry":10.0},{"gene":"RBM8A","stoichiometry":10.0},{"gene":"RPL11","stoichiometry":10.0},{"gene":"RPL13","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/RPLP1","total_profiled":1310},"omim":[{"mim_id":"180520","title":"RIBOSOMAL PROTEIN LATERAL STALK SUBUNIT P1; RPLP1","url":"https://www.omim.org/entry/180520"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Endoplasmic reticulum","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPLP1"},"hgnc":{"alias_symbol":["LP1","P1"],"prev_symbol":[]},"alphafold":{"accession":"P05386","domains":[{"cath_id":"1.10.10.1410","chopping":"3-63","consensus_level":"high","plddt":89.5687,"start":3,"end":63}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P05386","model_url":"https://alphafold.ebi.ac.uk/files/AF-P05386-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P05386-F1-predicted_aligned_error_v6.png","plddt_mean":69.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPLP1","jax_strain_url":"https://www.jax.org/strain/search?query=RPLP1"},"sequence":{"accession":"P05386","fasta_url":"https://rest.uniprot.org/uniprotkb/P05386.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P05386/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P05386"}},"corpus_meta":[{"pmid":"21040949","id":"PMC_21040949","title":"Expression of the ribosomal proteins Rplp0, Rplp1, and Rplp2 in gynecologic tumors.","date":"2010","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/21040949","citation_count":75,"is_preprint":false},{"pmid":"27974556","id":"PMC_27974556","title":"RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation.","date":"2017","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/27974556","citation_count":66,"is_preprint":false},{"pmid":"2784066","id":"PMC_2784066","title":"The human myeloma cell line LP-1: a versatile model in which to study early plasma-cell differentiation and c-myc activation.","date":"1989","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/2784066","citation_count":65,"is_preprint":false},{"pmid":"23541722","id":"PMC_23541722","title":"The multitarget opioid ligand LP1's effects in persistent pain and in primary cell neuronal 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Persistent Pain Relief.","date":"2021","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34299443","citation_count":11,"is_preprint":false},{"pmid":"36769010","id":"PMC_36769010","title":"RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36769010","citation_count":10,"is_preprint":false},{"pmid":"29734749","id":"PMC_29734749","title":"Synthesis and Structure-Activity Relationships of (-)-cis-N-Normetazocine-Based LP1 Derivatives.","date":"2018","source":"Pharmaceuticals (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/29734749","citation_count":8,"is_preprint":false},{"pmid":"17218011","id":"PMC_17218011","title":"Characterization of a cryptic plasmid from Bacillus sphaericus strain LP1-G.","date":"2007","source":"Plasmid","url":"https://pubmed.ncbi.nlm.nih.gov/17218011","citation_count":8,"is_preprint":false},{"pmid":"27052253","id":"PMC_27052253","title":"Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX.","date":"2016","source":"Frontiers of medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27052253","citation_count":8,"is_preprint":false},{"pmid":"28621109","id":"PMC_28621109","title":"Comparative Genomic Analysis of  GB-LP1 Isolated from Traditional Korean Fermented Food.","date":"2017","source":"Journal of microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/28621109","citation_count":8,"is_preprint":false},{"pmid":"39020429","id":"PMC_39020429","title":"Human umbilical cord mesenchymal stem cell-based gene therapy for hemophilia B using scAAV-DJ/8-LP1-hFIXco transduction.","date":"2024","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/39020429","citation_count":6,"is_preprint":false},{"pmid":"39032642","id":"PMC_39032642","title":"Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting.","date":"2024","source":"Molecular metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/39032642","citation_count":5,"is_preprint":false},{"pmid":"36776972","id":"PMC_36776972","title":"Vitellogenin receptor transports the 30K protein LP1 without cell-penetrating peptide, into the oocytes of the silkworm, Bombyx mori.","date":"2023","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/36776972","citation_count":5,"is_preprint":false},{"pmid":"19636829","id":"PMC_19636829","title":"A complete backbone spectral assignment of human apolipoprotein AI on a 38 kDa prebetaHDL (Lp1-AI) particle.","date":"2007","source":"Biomolecular NMR assignments","url":"https://pubmed.ncbi.nlm.nih.gov/19636829","citation_count":4,"is_preprint":false},{"pmid":"35129423","id":"PMC_35129423","title":"RPLP1, an NS4B-interacting protein, enhances production of CSFV through promoting translation of viral genome.","date":"2022","source":"Virulence","url":"https://pubmed.ncbi.nlm.nih.gov/35129423","citation_count":3,"is_preprint":false},{"pmid":"8866016","id":"PMC_8866016","title":"Regulation of the activity of M-phase promoting factor through protein kinase A-mediated pathway in LP1-1 cells.","date":"1996","source":"Biochemistry and molecular biology international","url":"https://pubmed.ncbi.nlm.nih.gov/8866016","citation_count":3,"is_preprint":false},{"pmid":"27624520","id":"PMC_27624520","title":"An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.","date":"2016","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27624520","citation_count":3,"is_preprint":false},{"pmid":"23469604","id":"PMC_23469604","title":"[Experimental research on the mechanisms of human multiple myeloma LP-1 cell apoptosis induced by oridonin].","date":"2012","source":"Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23469604","citation_count":3,"is_preprint":false},{"pmid":"6313465","id":"PMC_6313465","title":"Hepatocyte plasma membrane antigens. II. Characterization of liver-specific membrane lipoprotein (LP-1) and Tamm-Horsfall glycoprotein (THGP) like antigens (hepatic THGP) on the plasma membrane of Chang liver cell.","date":"1983","source":"Gastroenterologia Japonica","url":"https://pubmed.ncbi.nlm.nih.gov/6313465","citation_count":3,"is_preprint":false},{"pmid":"2851492","id":"PMC_2851492","title":"High-level expression of the simian virus 40 genes LP1, VP1 and VP2 as fusion proteins in Escherichia coli.","date":"1988","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/2851492","citation_count":2,"is_preprint":false},{"pmid":"14570274","id":"PMC_14570274","title":"Toxicity of Bacillus sphaericus LP1-G against susceptible and resistant Culex quinquefasciatus and the cloning of the mosquitocidal toxin gene.","date":"2003","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/14570274","citation_count":2,"is_preprint":false},{"pmid":"38985387","id":"PMC_38985387","title":"Beneficial Effect of Synbiotic Combination of Limosilactobacillus fermentum FS-10, Lactiplantibacillus plantarum Lp1-IC and Short-Chain Fructooligosaccharides in Colitis Murine Model.","date":"2024","source":"Probiotics and antimicrobial proteins","url":"https://pubmed.ncbi.nlm.nih.gov/38985387","citation_count":2,"is_preprint":false},{"pmid":"39936615","id":"PMC_39936615","title":"ESRRA (estrogen related receptor, alpha) induces ribosomal protein RPLP1-mediated adaptive hepatic translation during prolonged starvation.","date":"2025","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/39936615","citation_count":1,"is_preprint":false},{"pmid":"8038716","id":"PMC_8038716","title":"Allosteric interaction of a herpes simplex viral thymidine kinase with host DNA polymerase alpha in mouse LP1-1 cells.","date":"1994","source":"Biochemistry and molecular biology international","url":"https://pubmed.ncbi.nlm.nih.gov/8038716","citation_count":1,"is_preprint":false},{"pmid":"40889039","id":"PMC_40889039","title":"TMT-based proteomics analysis identifies RPLP1 as a key protein target in ursolic acid Inhibition of colorectal cancer.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40889039","citation_count":1,"is_preprint":false},{"pmid":"17343197","id":"PMC_17343197","title":"[The effect of cyclin D2 shRNA on the proliferation and apoptosis of LP-1 cell].","date":"2006","source":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","url":"https://pubmed.ncbi.nlm.nih.gov/17343197","citation_count":1,"is_preprint":false},{"pmid":"38260502","id":"PMC_38260502","title":"Estrogen receptor-related receptor (Esrra) induces ribosomal protein Rplp1-mediated adaptive hepatic translation during prolonged starvation.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38260502","citation_count":0,"is_preprint":false},{"pmid":"42223878","id":"PMC_42223878","title":"Functional and Genomic Characterization of a Human-Derived Lactiplantibacillus plantarum Strain LP1 with Activity Against Carbapenem-Resistant Enterobacterales.","date":"2026","source":"Probiotics and antimicrobial proteins","url":"https://pubmed.ncbi.nlm.nih.gov/42223878","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.11.28.625676","title":"Modelling the interaction between silver(I) ion and proteins with the 12-6 Lennard-Jones potential: a bottom-up parameterization approach","date":"2024-12-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.28.625676","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":28573,"output_tokens":3352,"usd":0.068,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10891,"output_tokens":3765,"usd":0.07429,"stage2_stop_reason":"end_turn"},"total_usd":0.14229,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"RPLP1 and RPLP2 form the ribosomal stalk by binding to RPLP0, and are specifically required for flavivirus (DENV, YFV, ZIKV) translation; knockdown strongly reduced early viral protein accumulation and reduced DENV structural proteins expressed from an exogenous transgene, implicating RPLP1/2 in translation elongation through the viral open reading frame.\",\n      \"method\": \"RNA interference knockdown, metabolic labeling of global protein synthesis, exogenous transgene expression assay, in two human cell lines (A549, HuH-7) and Aedes aegypti mosquitoes\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — validated in multiple cell lines and in vivo mosquito model with multiple orthogonal methods (RNAi, metabolic labeling, transgene reporter), replicated across biological contexts\",\n      \"pmids\": [\"27974556\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RPLP1 and RPLP2 relieve ribosome pausing within sequences encoding multiple adjacent transmembrane domains (TMDs); ribosome profiling in RPLP1/2-depleted cells showed ribosome pausing immediately downstream of sequences encoding two adjacent TMDs in the DENV envelope protein, and RPLP1/2 depletion disproportionately affected ribosome density on cellular mRNAs encoding multiple TMDs, implicating RPLP1/2 in co-translational folding and biogenesis of multi-pass transmembrane proteins.\",\n      \"method\": \"Ribosome profiling in RPLP1/2-depleted cells, siRNA knockdown, viral and cellular mRNA translation analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — ribosome profiling with genome-wide resolution, mechanistic follow-up on both viral and cellular substrates, multiple orthogonal analyses in a single rigorous study\",\n      \"pmids\": [\"32890404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPLP1 inhibits transcription of clade B HIV-1 by occupying C/EBPβ binding sites in the viral long terminal repeat (LTR); this interaction requires α-helices 2 and 4 of RPLP1; HIV-1 infection induces translocation of RPLP1 from the cytoplasm to the nucleus, which is essential for its antiviral activity; RPLP1 knockdown promotes reactivation of latent HIV-1 proviruses.\",\n      \"method\": \"Chromatin binding assays, domain mutagenesis (α-helix deletion), subcellular fractionation/confocal imaging for nuclear translocation, shRNA knockdown with latency reactivation assay, LTR reporter assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods including domain mutagenesis, localization studies, reporter assays, and latency reactivation in a single rigorous study\",\n      \"pmids\": [\"38906865\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Rplp1 is essential for embryonic nervous system development; conditional knockout in the CNS (Rplp1CNSΔ) caused perinatal lethality, brain atrophy, progenitor cell proliferation arrest and apoptosis with dysregulation of cyclin A, cyclin E, p21CIP1, p27KIP1, and p53; Rplp1 deletion in primary mouse embryonic fibroblasts (pMEFs) did not alter global protein synthesis but changed expression patterns of specific protein subsets involved in protein folding, unfolded protein response, cell death, and signal transduction, demonstrating translational 'fine-tuning'.\",\n      \"method\": \"Germline and conditional CNS knockout mouse, immunohistochemistry, western blot, 2D-DIGE proteomics of pMEFs, cell cycle and apoptosis analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo genetic knockout combined with multiple orthogonal cellular and proteomic readouts establishing functional mechanism\",\n      \"pmids\": [\"24959908\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Overexpression of Rplp1 bypasses replicative senescence in primary mouse embryonic fibroblasts, producing a two-fold increase in E2F1 promoter activity and upregulation of cyclin E; co-expression with mutant RasVal12 contributes to transformation in NIH3T3 cells; p53 dominant-negative mutant (p53R175H) upregulates Rplp1, suggesting p53 mutation facilitates immortalization via Rplp1.\",\n      \"method\": \"ES cell cDNA library screen, retroviral overexpression in MEFs, E2F1 promoter luciferase assay, western blot for cyclin E, soft-agar colony formation assay with RasVal12 co-expression\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays (promoter reporter, transformation assay, Western blot) in a single lab with clear mechanistic readouts\",\n      \"pmids\": [\"19233166\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The transcription factor ESRRA (estrogen-related receptor alpha) transcriptionally activates the Rplp1 gene promoter; decreased ESRRA binding to the Rplp1 promoter during lipotoxicity reduces Rplp1 expression, which in turn reduces global protein translation and specifically impairs translation of lysosome proteins (Lamp2, Ctsd) and autophagy proteins (sqstm1, Map1lc3b); ESRRA does not directly increase binding to lysosome/autophagy gene promoters, confirming its regulation is at the translational level via Rplp1.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) for ESRRA at Rplp1 promoter, siRNA/overexpression of Esrra and Rplp1, puromycin labeling of global translation, polysome profiling, proteomics in human primary hepatocytes, mouse AML12 cells, and in vivo mouse MASH model\",\n      \"journal\": \"Molecular metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — ChIP, polysome profiling, and proteomics with in vitro and in vivo validation across multiple model systems, orthogonal mechanistic approaches\",\n      \"pmids\": [\"39032642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"During prolonged starvation, ESRRA increases and transcriptionally stimulates Rplp1 gene expression to drive selective adaptive translation of lysosome and autolysosome proteins, thereby activating autophagy; Esrra overexpression or siRNA knockdown caused parallel changes in Rplp1 expression, lysosome/autophagy protein translation, and autophagy activity in vitro and in vivo.\",\n      \"method\": \"siRNA knockdown and overexpression of Esrra in vitro and in vivo, proteomic analysis, polysome profiling, mRNA transcription analysis, autophagy flux assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (proteomics, polysome profiling, transcriptomics, autophagy assays) replicated in vitro and in vivo in liver-specific Esrra knockout mice\",\n      \"pmids\": [\"39936615\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RPLP1 physically interacts with CSFV (classical swine fever virus) NS4B protein, as confirmed by co-immunoprecipitation, GST pulldown, and confocal co-localization; RPLP1 knockdown reduced viral protein expression and progeny virus titers without affecting CSFV IRES activity or intracellular viral RNA abundance, indicating RPLP1 promotes CSFV genome translation post-entry.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, confocal microscopy, lentiviral shRNA knockdown, overexpression, dual-luciferase IRES reporter assay, viral titer measurement\",\n      \"journal\": \"Virulence\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding validated by three methods (Co-IP, GST pulldown, confocal), functional consequences assessed by multiple assays in a single lab\",\n      \"pmids\": [\"35129423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RPLP1 is essential for endometriotic epithelial cell survival in vitro; stable shRNA knockdown of RPLP1 in an endometriosis cell line resulted in a significant decrease in cell survival.\",\n      \"method\": \"shRNA stable knockdown, cell survival assay, immunohistochemistry, western blotting, qRT-PCR in tissue specimens and cell lines\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotype, corroborated by tissue expression data, single lab\",\n      \"pmids\": [\"31899515\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RPLP1 knockdown in endometrial adenocarcinoma cell lines reduced cell survival and migration, establishing a role for RPLP1 in mediating these processes in endometrial cancer cells.\",\n      \"method\": \"siRNA knockdown in multiple endometrial adenocarcinoma cell lines (Ishikawa, HEC1A, HEC1B, AN3), cell survival and migration assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype in multiple cell lines, single lab\",\n      \"pmids\": [\"36769010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CNN3 promotes the viability and motility of cervical cancer cells partly through downstream regulation of RPLP1 mRNA expression; rescue experiments showed that RPLP1 overexpression reversed phenotypes inhibited by CNN3 silencing, placing RPLP1 downstream of CNN3 in this pathway.\",\n      \"method\": \"RNA sequencing to identify downstream genes, siRNA knockdown of CNN3, RPLP1 overexpression rescue experiments, proliferation/migration/invasion assays, xenograft model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established by rescue experiment, multiple functional assays and in vivo validation, single lab\",\n      \"pmids\": [\"32051425\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Giant panda RPLP1 protein contains three casein kinase II phosphorylation sites and two N-myristoylation sites, as predicted by topology analysis; the recombinant His-tagged RPLP1 protein was expressed in E. coli as an ~18 kDa polypeptide consistent with predictions.\",\n      \"method\": \"RT-PCR cloning, sequence alignment, topology/modification site prediction, recombinant expression in E. coli\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction of modification sites with no experimental validation of phosphorylation or myristoylation\",\n      \"pmids\": [\"18071584\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPLP1 is a component of the ribosomal stalk (formed with RPLP0 and RPLP2) that functions primarily to relieve ribosome pausing at sequences encoding multiple transmembrane domains, thereby promoting translation elongation and co-translational folding of multi-pass transmembrane proteins; it is transcriptionally induced by ESRRA to drive selective adaptive translation of lysosomal and autophagy proteins during starvation; it can translocate from cytoplasm to nucleus to restrict HIV-1 transcription by occupying C/EBPβ binding sites in the viral LTR; and it is required for efficient translation of flaviviral and other viral genomes, while also promoting cell survival and migration in multiple cancer contexts.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPLP1 is a component of the ribosomal stalk that, together with RPLP2, assembles onto RPLP0 to regulate translation elongation, with a specialized role in relieving ribosome pausing within sequences encoding multiple adjacent transmembrane domains, thereby supporting co-translational folding and biogenesis of multi-pass transmembrane proteins [#0, #1]. Rather than governing bulk protein synthesis, RPLP1 acts as a translational 'fine-tuner': its loss in primary fibroblasts leaves global translation unchanged but reshapes the expression of defined protein subsets, and its deletion in the developing CNS causes progenitor proliferation arrest, apoptosis, and dysregulation of cell-cycle regulators, establishing an essential role in nervous system development [#3]. This selective translational function is harnessed for metabolic adaptation: the transcription factor ESRRA binds and activates the Rplp1 promoter, and ESRRA-driven RPLP1 expression selectively promotes translation of lysosomal and autophagy proteins to activate autophagy during starvation and lipotoxic stress [#5, #6]. RPLP1 is also exploited by diverse viruses, being required for the elongation phase of flaviviral and classical swine fever virus genome translation through interactions with viral proteins, while a separate nuclear pool restricts HIV-1 by occupying C/EBPβ binding sites in the viral LTR [#0, #1, #2, #7]. Across several cancer contexts, RPLP1 promotes cell survival and migration [#9, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established a pro-proliferative, immortalizing activity for RPLP1 distinct from a passive structural role, linking it to cell-cycle control.\",\n      \"evidence\": \"Retroviral overexpression in MEFs with E2F1 promoter reporter, cyclin E western blot, and Ras co-transformation/soft-agar assays\",\n      \"pmids\": [\"19233166\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish whether the effect is mediated through ribosomal/translational function or an extra-ribosomal activity\", \"Mechanistic link to E2F1/cyclin E is correlative\", \"Single-lab overexpression system\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed RPLP1 is required for development and acts by translational fine-tuning of specific protein subsets rather than bulk synthesis, answering whether stalk loss equals global translation failure.\",\n      \"evidence\": \"Germline and conditional CNS knockout mice with immunohistochemistry, and 2D-DIGE proteomics of knockout pMEFs\",\n      \"pmids\": [\"24959908\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the direct mRNA targets selectively affected was not defined\", \"Mechanism connecting stalk function to cell-cycle regulator dysregulation unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined RPLP1 as a stalk subunit (with RPLP2 on RPLP0) specifically required for flavivirus genome translation, framing it as an elongation-phase factor.\",\n      \"evidence\": \"RNAi knockdown with metabolic labeling and transgene reporter assays in A549/HuH-7 cells and Aedes aegypti mosquitoes\",\n      \"pmids\": [\"27974556\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not yet define why viral ORFs are selectively dependent on RPLP1/2\", \"No structural detail of stalk assembly in this context\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified the molecular basis of RPLP1/2 selectivity: relief of ribosome pausing at sequences encoding adjacent transmembrane domains, explaining its preferential effect on multi-pass membrane proteins and viral structural proteins.\",\n      \"evidence\": \"Ribosome profiling in RPLP1/2-depleted cells with analysis of viral and cellular TMD-encoding mRNAs\",\n      \"pmids\": [\"32890404\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural mechanism by which the stalk resolves TMD-associated pausing not determined\", \"Whether co-translational folding machinery is directly engaged not shown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended RPLP1's survival function to disease tissue, showing it is required for endometriotic epithelial cell survival.\",\n      \"evidence\": \"Stable shRNA knockdown with cell survival assays plus tissue expression analysis\",\n      \"pmids\": [\"31899515\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway linking RPLP1 to survival not defined\", \"Single cell-line phenotype\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placed RPLP1 downstream of CNN3 in a cervical cancer proliferation/migration pathway via epistasis.\",\n      \"evidence\": \"RNA-seq identification, CNN3 knockdown with RPLP1 overexpression rescue, functional assays and xenograft\",\n      \"pmids\": [\"32051425\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How CNN3 regulates RPLP1 mRNA is unknown\", \"Whether RPLP1's effect requires its ribosomal function not addressed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated a direct physical interaction between RPLP1 and a viral protein (CSFV NS4B) and that RPLP1 supports viral genome translation post-entry independent of IRES activity.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, GST pulldown, confocal co-localization, shRNA knockdown, dual-luciferase IRES reporter, and viral titer measurement\",\n      \"pmids\": [\"35129423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional significance of the NS4B interaction for translation is not mechanistically resolved\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Generalized RPLP1's pro-tumor role, showing it mediates survival and migration across multiple endometrial cancer cell lines.\",\n      \"evidence\": \"siRNA knockdown in four endometrial adenocarcinoma lines with survival and migration assays\",\n      \"pmids\": [\"36769010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream effectors not identified\", \"Does not distinguish ribosomal from non-ribosomal mechanism\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified ESRRA as a transcriptional driver of Rplp1 and showed this axis selectively controls translation of lysosomal and autophagy proteins, linking RPLP1 to metabolic stress responses.\",\n      \"evidence\": \"ChIP for ESRRA at the Rplp1 promoter, Esrra/Rplp1 perturbation, puromycin labeling, polysome profiling, and proteomics across hepatocytes, AML12 cells, and a mouse MASH model\",\n      \"pmids\": [\"39032642\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"mRNA features that confer selective RPLP1 dependence of lysosome/autophagy transcripts not defined\", \"Relationship to the TMD-pausing mechanism not addressed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a non-canonical nuclear function: HIV-1-induced cytoplasm-to-nucleus translocation of RPLP1 represses viral transcription by occupying C/EBPβ sites in the LTR, and its loss reactivates latent provirus.\",\n      \"evidence\": \"Chromatin binding assays, α-helix deletion mutagenesis, subcellular fractionation/confocal imaging, LTR reporter assays, and shRNA knockdown with latency reactivation\",\n      \"pmids\": [\"38906865\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger and machinery for nuclear translocation not defined\", \"How a stalk protein acquires sequence-specific DNA occupancy at C/EBPβ sites is unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Consolidated the ESRRA-RPLP1 axis as a starvation-responsive program that drives selective adaptive translation of lysosome/autolysosome proteins to activate autophagy.\",\n      \"evidence\": \"Esrra perturbation in vitro and in vivo (liver-specific Esrra knockout mice), proteomics, polysome profiling, transcriptomics, and autophagy flux assays\",\n      \"pmids\": [\"39936615\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct demonstration that RPLP1 stalk activity (not abundance alone) confers selectivity is incomplete\", \"Connection to membrane-protein biogenesis mechanism not integrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how a single ribosomal stalk subunit reconciles its distinct activities — relief of TMD ribosome pausing, selective translation of lysosome/autophagy proteins, viral genome translation, and sequence-specific nuclear transcriptional repression — and what structural features or post-translational signals partition RPLP1 between these roles.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model linking stalk function to substrate selectivity\", \"Signals controlling cytoplasm-to-nucleus partitioning undefined\", \"Predicted phosphorylation/myristoylation sites lack experimental validation\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-72766\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 2, 7]}\n    ],\n    \"complexes\": [\"ribosomal stalk\"],\n    \"partners\": [\"RPLP0\", \"RPLP2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}