{"gene":"RPLP0","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":1999,"finding":"Ribosomal protein L10e (uL10/RPLP0) is required for sordarin sensitivity in yeast; mutations in a conserved 10-amino acid region of L10e confer resistance to the eEF2 inhibitor sordarin by reducing sordarin-stabilized eEF2-nucleotide-ribosome complex formation, establishing a functional linkage between L10e and translocation by eEF2.","method":"Biochemical and molecular genetic analysis of sordarin-resistant mutants; sequencing of L10e alleles; in vitro eEF2-ribosome-nucleotide complex stabilization assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro biochemical assay combined with mutagenesis identifying causal residues, replicated across multiple alleles","pmids":["9988728"],"is_preprint":false},{"year":1995,"finding":"Ricin A chain physically cross-links to ribosomal proteins L9 and L10e (RPLP0) on mammalian ribosomes, identifying L10e as a ribosome-surface component accessible to the toxin; ricin A chain localizes to the endoplasmic reticulum and nucleoli in permeabilized cells.","method":"Chemical cross-linking with 125I-labeled ricin A chain on purified mammalian ribosomes; tryptic peptide sequencing; indirect immunofluorescence; competition with excess unlabeled ricin A chain as specificity control","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro cross-linking on purified ribosomes with sequence-level identification of the binding partner and rigorous specificity controls","pmids":["7759553"],"is_preprint":false},{"year":1991,"finding":"In the archaebacterium Sulfolobus solfataricus, L10e (uL10) is a near neighbor of L12e (the L7/L12 homolog) in the large ribosomal subunit, forming part of a pentameric (L12e)4–L10e complex that constitutes the factor-binding domain; this organization is conserved across eubacteria, archaea, and eukaryotes.","method":"Chemical cross-linking with 2-iminothiolane; two-dimensional diagonal SDS-PAGE; N-terminal sequencing of cross-linked partners","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous in vitro cross-linking and sequencing in a single study on an archaeal ortholog; functional conservation inferred but not directly tested in mammalian cells","pmids":["1939187"],"is_preprint":false},{"year":2002,"finding":"Overexpression of yeast ribosomal protein Rpp0 (uL10/RPLP0 ortholog) cures prion determinants [PSI+PS] and [PSI+] in a prion-strain-specific manner, at least partly by modulating chaperone-related promoter activity (SSA4, HSP104).","method":"Multicopy yeast genomic library screen; prion curing assays; promoter-reporter assays for chaperone gene expression","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional genetic screen plus reporter assays in yeast ortholog, multiple prion strains tested","pmids":["11923285"],"is_preprint":false},{"year":2017,"finding":"Upon nucleolar stress, the uL10 (RPLP0) protein is released from pre-existing ribosomes and accumulates in the cytoplasm as a ribosome-free pool in mammalian cells, indicating a stress-responsive regulatory role beyond translation.","method":"Biochemical fractionation; advanced fluorescence microscopy; FRAP after photoconversion (FRAP-AC) in mammalian cells","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (fractionation + live-cell FRAP-AC) in mammalian cells demonstrating ribosome release under stress","pmids":["28986221"],"is_preprint":false},{"year":2020,"finding":"Phosphorylation within the N-terminal rRNA-binding domain of uL10 (RPLP0) impairs its association with the ribosome; introduction of a negative charge at N-terminal sites reduces ribosome binding, revealing a phosphorylation-dependent regulatory mechanism governing P-stalk assembly and GTPase-associated center activity.","method":"Phosphorylation site mapping; mutagenesis introducing negative charge mimics; ribosome association assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis combined with functional ribosome-binding assay in a single study","pmids":["32668052"],"is_preprint":false},{"year":2019,"finding":"The extended protuberant (uL10ext) domain of eukaryotic uL10 (RPLP0) contains a conserved 'hinge' region around Phe183 that undergoes conformational rearrangement; substitution of the equivalent yeast residue (F181A) increases polyphenylalanine synthesis ~33% in an in vitro translation assay, demonstrating that hinge motion facilitates binding of translation factors to the GTPase-associated center.","method":"NMR structure determination (solution structure of uL10ext domain from Bombyx mori); 15N relaxation analysis; yeast mutant strain construction; in vitro translation assay","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — structure plus mutagenesis plus in vitro functional assay in a single rigorous study","pmids":["31419120"],"is_preprint":false},{"year":2014,"finding":"RPLP0 interacts with cathepsin X/Z (CTSX) in gastric cancer cells; knockdown of RPLP0 causes G1 cell cycle arrest and down-regulates CDK2, and affects p21 expression (but not Cyclin E), placing RPLP0 as an anti-apoptotic regulator; CTSX knockdown causes nuclear translocation of RPLP0.","method":"Yeast two-hybrid; co-immunoprecipitation; co-localization by laser-scan microscopy; siRNA knockdown; cell cycle analysis; western blotting","journal":"Pathology, research and practice","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP confirming interaction, plus knockdown with defined molecular phenotype (CDK2, p21), single lab","pmids":["25433997"],"is_preprint":false},{"year":2019,"finding":"RPLP0 physically interacts with the tumor suppressor PLAAT4; RPLP0 protein levels are suppressed in PLAAT4-expressing cells, and RPLP0 silencing phenocopies PLAAT4 expression (decreased viability, reduced cell-cycle and anti-apoptotic proteins), indicating RPLP0 mediates PLAAT4-induced cell cycle arrest and apoptosis.","method":"Yeast two-hybrid screening; co-immunoprecipitation; co-localization; siRNA knockdown; cell viability assays; western blotting","journal":"Cell biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus co-IP confirming interaction, plus knockdown phenocopy, single lab","pmids":["31131438"],"is_preprint":false},{"year":2010,"finding":"RPLP0 functions as a cell-surface receptor on mammary endothelial cells during lactation, mediating binding and internalization of the MG1 homing peptide (CLHQHNQMC) identified by in vivo phage display.","method":"In vivo phage display biopanning; peptide affinity pull-down assay; immunoblotting; in vitro endothelial cell internalization assay; competitive inhibition with synthetic peptide","journal":"Peptides","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pull-down plus functional internalization assay with competitive inhibition control; surface localization of a classically cytoplasmic protein is unusual and warrants caution","pmids":["20863866"],"is_preprint":false},{"year":2022,"finding":"An alternatively spliced isoform of uL10 (named uL10β) is stably expressed in mammalian cells, localizes predominantly to the nucleus, can associate with 60S and 80S ribosomal particles, and undergoes re-localization to mitochondria upon ER stress, suggesting a specialized stress-related function.","method":"RT-PCR/sequencing of isoform; subcellular fractionation; fluorescence microscopy; ribosome sedimentation assays; ER stress induction experiments","journal":"Biochimica et biophysica acta. Gene regulatory mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (fractionation, imaging, sucrose gradient) in a single study characterizing a novel isoform","pmids":["36328276"],"is_preprint":false},{"year":2008,"finding":"Overexpression of yeast RPP0 (RPLP0 ortholog) enhances secretion of heterologous proteins; the effect does not appear to involve ribosome function directly, but instead RPP0 overexpression prevents upregulation of the yeast plasma membrane H+-ATPase gene PMA1, thereby limiting medium acidification.","method":"Gene overexpression in S. cerevisiae; secretion yield assays; gene expression analysis of PMA1","journal":"Biotechnology progress","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect mechanistic inference from expression data for PMA1 link, no direct biochemical confirmation","pmids":["18396911"],"is_preprint":false},{"year":2024,"finding":"RPLP0 knockdown activates apoptosis signaling in human umbilical vein endothelial cells and enhances endothelial permeability; TNF-α treatment combined with RPLP0 knockdown synergistically increases these effects, placing RPLP0 as an anti-apoptotic factor in endothelial cells relevant to high-altitude pulmonary edema.","method":"In vivo HAPE rat model validation; siRNA knockdown in HUVECs; apoptosis assays; permeability assays","journal":"Apoptosis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional knockdown with defined cellular readout but no detailed molecular pathway dissection; single study","pmids":["39110356"],"is_preprint":false},{"year":2024,"finding":"RPLP0 promotes HCC cell proliferation, invasion, and migration partly through activation of the JAK/STAT3 pathway; miR-450b-5p directly targets the RPLP0 3'UTR (validated by luciferase reporter assay) to downregulate RPLP0 and suppress this pathway.","method":"Luciferase reporter assay; siRNA knockdown; xenograft tumor assay; western blotting for JAK/STAT3 pathway components","journal":"Translational oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, pathway association by knockdown without biochemical reconstitution of RPLP0-JAK/STAT3 link","pmids":["39383650"],"is_preprint":false},{"year":2025,"finding":"c-Myc directly binds the RPLP0 promoter and activates its transcription; RPLP0 in turn activates the JAK2/STAT3 pathway via ROS suppression, which upregulates c-Myc, forming a positive feedback loop driving HCC progression.","method":"Chromatin immunoprecipitation (ChIP); dual luciferase promoter assay; siRNA knockdown; ROS measurement; western blotting for JAK2/STAT3/c-Myc","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus luciferase assay establish direct transcriptional regulation; knockdown experiments with pathway readouts; single lab","pmids":["41312719"],"is_preprint":false}],"current_model":"RPLP0 (uL10) is the core scaffold of the ribosomal P-stalk in the GTPase-associated center (GAC), anchoring P1/P2 heterodimers to the 60S subunit via its N-terminal rRNA-binding domain; N-terminal phosphorylation of uL10 negatively regulates its ribosome association, providing a regulatory switch for GAC activity; a conserved 'hinge' motion in its extended protuberant domain facilitates sequential binding of translational GTPases (eEF2, eRF1) required for translocation and termination; under nucleolar stress, uL10 is released from ribosomes as a free cytoplasmic pool; an alternatively spliced isoform (uL10β) localizes primarily to the nucleus and redistributes to mitochondria upon ER stress; beyond translation, RPLP0 interacts with cathepsin X/Z and PLAAT4 to modulate cell cycle progression and apoptosis (via CDK2/p21), is transcriptionally activated by c-Myc and reciprocally sustains a JAK2/STAT3/c-Myc feedback loop in cancer cells, and was identified as a cell-surface receptor on mammary endothelial cells mediating peptide internalization during lactation."},"narrative":{"mechanistic_narrative":"RPLP0 (uL10) is the core scaffold of the ribosomal P-stalk in the GTPase-associated center (GAC) of the large subunit, the platform that recruits translational GTPases for elongation and termination [PMID:9988728, PMID:1939187]. In the archaeal and conserved organization, uL10 nucleates a pentameric (P-protein)4–uL10 factor-binding complex adjacent to the L7/L12 (P1/P2) homologs [PMID:1939187], and it sits at a ribosome-surface position accessible to exogenous ligands, as shown by direct cross-linking of ricin A chain to L10e on mammalian ribosomes [PMID:7759553]. Functionally, uL10 is coupled to eEF2-driven translocation: mutations in a conserved region confer resistance to the eEF2 inhibitor sordarin by destabilizing the eEF2–nucleotide–ribosome complex [PMID:9988728], and a conserved 'hinge' around Phe183 in the extended protuberant (uL10ext) domain undergoes conformational rearrangement that gates factor binding, since hinge mutation increases in vitro polyphenylalanine synthesis [PMID:31419120]. P-stalk assembly is regulated by phosphorylation within the N-terminal rRNA-binding domain, which introduces negative charge that impairs ribosome association and thereby tunes GAC activity [PMID:32668052]. Beyond steady-state translation, uL10 is released from pre-existing ribosomes into a free cytoplasmic pool under nucleolar stress [PMID:28986221], and an alternatively spliced isoform (uL10β) localizes predominantly to the nucleus, associates with 60S/80S particles, and redistributes to mitochondria upon ER stress [PMID:36328276]. Extra-ribosomal activities have also been reported: RPLP0 binds cathepsin X/Z (CTSX) and the tumor suppressor PLAAT4 to influence G1 progression and apoptosis through CDK2/p21 [PMID:25433997, PMID:31131438], and c-Myc directly activates RPLP0 transcription while RPLP0 sustains a JAK2/STAT3/c-Myc feedback loop in hepatocellular carcinoma [PMID:41312719].","teleology":[{"year":1991,"claim":"Establishing where uL10 sits in the ribosome was the first step in defining its function; cross-linking placed it as a near neighbor of the L12e (P1/P2) proteins within the conserved factor-binding domain.","evidence":"2-iminothiolane cross-linking and N-terminal sequencing of the (L12e)4–L10e complex in archaeal ribosomes","pmids":["1939187"],"confidence":"Medium","gaps":["Conservation to mammalian ribosomes inferred but not directly tested here","Does not establish how uL10 engages translational GTPases functionally"]},{"year":1995,"claim":"Cross-linking of ricin A chain confirmed L10e/RPLP0 is a surface-exposed component of mammalian ribosomes, anchoring the archaeal organization in the mammalian context.","evidence":"Chemical cross-linking of 125I-ricin A chain on purified mammalian ribosomes with tryptic peptide sequencing and competition controls","pmids":["7759553"],"confidence":"High","gaps":["Does not define the catalytic or factor-recruitment role of L10e","Functional consequence of the ricin-uL10 proximity not established"]},{"year":1999,"claim":"Linking uL10 to translocation: sordarin-resistance mutations showed L10e is functionally coupled to eEF2-mediated elongation, not merely structural.","evidence":"Sordarin-resistant L10e allele sequencing and in vitro eEF2–ribosome–nucleotide complex stabilization assays in yeast","pmids":["9988728"],"confidence":"High","gaps":["Does not resolve the structural mechanism of factor engagement","Limited to eEF2; other GTPases not addressed in this study"]},{"year":2002,"claim":"A yeast genetic screen revealed an unexpected link between the uL10 ortholog and prion propagation via chaperone gene expression, hinting at functions beyond translation.","evidence":"Multicopy genomic library screen, prion-curing assays, and chaperone promoter-reporter assays in yeast","pmids":["11923285"],"confidence":"Medium","gaps":["Mechanism connecting Rpp0 overexpression to chaperone promoters unresolved","Relevance to mammalian RPLP0 untested"]},{"year":2010,"claim":"RPLP0 was identified at the cell surface acting as a receptor for a homing peptide, an unusual extra-ribosomal localization.","evidence":"In vivo phage display, peptide affinity pull-down, and endothelial internalization assay with competitive inhibition","pmids":["20863866"],"confidence":"Medium","gaps":["Surface display of a classically cytoplasmic protein not mechanistically explained","No structural basis for peptide recognition"]},{"year":2014,"claim":"Identification of RPLP0–cathepsin X/Z interaction and a CDK2/p21-linked cell-cycle phenotype framed RPLP0 as an anti-apoptotic, cell-cycle regulator in cancer cells.","evidence":"Yeast two-hybrid, reciprocal co-IP, co-localization, siRNA knockdown, and cell cycle analysis in gastric cancer cells","pmids":["25433997"],"confidence":"Medium","gaps":["Whether the cell-cycle effect is ribosome-dependent or extra-ribosomal unclear","Direct biochemical mechanism linking RPLP0 to CDK2/p21 not defined"]},{"year":2017,"claim":"Demonstrating stress-induced release answered whether uL10 is a static subunit: under nucleolar stress it exits ribosomes to form a free cytoplasmic pool.","evidence":"Biochemical fractionation and FRAP after photoconversion (FRAP-AC) in mammalian cells","pmids":["28986221"],"confidence":"High","gaps":["Function of the free cytoplasmic pool not established","Trigger linking nucleolar stress to release mechanistically undefined"]},{"year":2019,"claim":"Two studies refined uL10 mechanism: a conserved Phe183 'hinge' in the uL10ext domain gates translation-factor binding, and a PLAAT4 interaction tied RPLP0 to tumor-suppressor-induced apoptosis.","evidence":"NMR solution structure with 15N relaxation plus yeast F181A mutant and in vitro translation; and yeast two-hybrid/co-IP/knockdown phenocopy for PLAAT4","pmids":["31419120","31131438"],"confidence":"High","gaps":["How hinge dynamics coordinate sequential eEF2/eRF1 binding not directly resolved","PLAAT4–RPLP0 mechanism (single-lab) lacks reciprocal in vivo validation"]},{"year":2020,"claim":"Identifying N-terminal phosphorylation as a switch showed P-stalk assembly is actively regulated: negative charge in the rRNA-binding domain impairs ribosome association.","evidence":"Phosphosite mapping, phosphomimetic mutagenesis, and ribosome association assays","pmids":["32668052"],"confidence":"Medium","gaps":["Kinase responsible not identified","Physiological conditions driving phosphorylation undefined"]},{"year":2022,"claim":"Characterization of the uL10β splice isoform revealed a nuclear-localizing, ribosome-associating variant that relocates to mitochondria under ER stress, expanding the functional repertoire.","evidence":"Isoform RT-PCR/sequencing, subcellular fractionation, imaging, and ribosome sedimentation with ER stress induction","pmids":["36328276"],"confidence":"Medium","gaps":["Function of mitochondrial relocalization unknown","Whether uL10β supports translation distinct from canonical uL10 untested"]},{"year":2025,"claim":"Integration into a transcriptional circuit: c-Myc directly activates RPLP0, which sustains JAK2/STAT3 via ROS suppression to reinforce c-Myc, defining a feedback loop in HCC; related work tied RPLP0 to endothelial apoptosis and miR-450b-5p regulation.","evidence":"ChIP and dual-luciferase promoter assays with ROS measurement and pathway westerns; plus knockdown studies in HUVECs and HCC with luciferase 3'UTR targeting","pmids":["41312719","39110356","39383650"],"confidence":"Medium","gaps":["Direct biochemical link between RPLP0 and JAK2/STAT3 not reconstituted","Whether the cancer roles depend on ribosomal vs extra-ribosomal RPLP0 unresolved"]},{"year":null,"claim":"How RPLP0's canonical P-stalk function mechanistically connects to its reported extra-ribosomal roles in cell-cycle control, apoptosis, and oncogenic signaling remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biochemical bridge between the free/nuclear pool and signaling functions","Kinases, recruitment factors, and stress sensors governing relocalization unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,1]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[5]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[0,6]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[1,2,10]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[7,10]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[10]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,6]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[4,10]}],"complexes":["ribosomal P-stalk / GTPase-associated center"],"partners":["RPLP1","RPLP2","EEF2","CTSZ","PLAAT4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P05388","full_name":"Large ribosomal subunit protein uL10","aliases":["60S acidic ribosomal protein P0","60S ribosomal protein L10E"],"length_aa":317,"mass_kda":34.3,"function":"Ribosomal protein P0 is the functional equivalent of E.coli protein L10","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P05388/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPLP0","classification":"Common Essential","n_dependent_lines":1206,"n_total_lines":1208,"dependency_fraction":0.9983443708609272},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RPLP0","total_profiled":1310},"omim":[{"mim_id":"620476","title":"MRT4 HOMOLOG, RIBOSOME MATURATION FACTOR; MRTO4","url":"https://www.omim.org/entry/620476"},{"mim_id":"400012","title":"VARIABLY CHARGED, Y CHROMOSOME; VCY","url":"https://www.omim.org/entry/400012"},{"mim_id":"180510","title":"RIBOSOMAL PROTEIN LATERAL STALK SUBUNIT P0; RPLP0","url":"https://www.omim.org/entry/180510"}],"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/RPLP0"},"hgnc":{"alias_symbol":["PRLP0","P0","L10E","RPP0","LP0","uL10"],"prev_symbol":[]},"alphafold":{"accession":"P05388","domains":[{"cath_id":"3.30.70.1730","chopping":"5-106_186-204","consensus_level":"high","plddt":89.2521,"start":5,"end":204},{"cath_id":"3.90.105.20","chopping":"114-181","consensus_level":"high","plddt":89.7607,"start":114,"end":181},{"cath_id":"-","chopping":"207-269","consensus_level":"high","plddt":85.2963,"start":207,"end":269}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P05388","model_url":"https://alphafold.ebi.ac.uk/files/AF-P05388-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P05388-F1-predicted_aligned_error_v6.png","plddt_mean":79.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPLP0","jax_strain_url":"https://www.jax.org/strain/search?query=RPLP0"},"sequence":{"accession":"P05388","fasta_url":"https://rest.uniprot.org/uniprotkb/P05388.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P05388/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P05388"}},"corpus_meta":[{"pmid":"1846207","id":"PMC_1846207","title":"The open reading frames UL3, UL4, UL10, and UL16 are dispensable for the replication of herpes simplex virus 1 in cell culture.","date":"1991","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/1846207","citation_count":161,"is_preprint":false},{"pmid":"7679747","id":"PMC_7679747","title":"The UL10 gene of herpes simplex virus 1 encodes a novel viral glycoprotein, gM, which is present in the virion and in the plasma membrane of infected cells.","date":"1993","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/7679747","citation_count":116,"is_preprint":false},{"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":"11923285","id":"PMC_11923285","title":"Increased expression of Hsp40 chaperones, transcriptional factors, and ribosomal protein 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identification of a novel delayed-early gene product, OBPC.","date":"1994","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/8207800","citation_count":51,"is_preprint":false},{"pmid":"10466817","id":"PMC_10466817","title":"DNA sequence of the UL6 to UL20 genes of infectious laryngotracheitis virus and characterization of the UL10 gene product as a nonglycosylated and nonessential virion protein.","date":"1999","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/10466817","citation_count":47,"is_preprint":false},{"pmid":"9988728","id":"PMC_9988728","title":"Mutations in ribosomal protein L10e confer resistance to the fungal-specific eukaryotic elongation factor 2 inhibitor sordarin.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9988728","citation_count":47,"is_preprint":false},{"pmid":"25433997","id":"PMC_25433997","title":"Dysregulation of apoptotic signaling pathways by interaction of RPLP0 and cathepsin X/Z in gastric cancer.","date":"2014","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/25433997","citation_count":42,"is_preprint":false},{"pmid":"7759553","id":"PMC_7759553","title":"Ricin A chain can be chemically cross-linked to the mammalian ribosomal proteins L9 and L10e.","date":"1995","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7759553","citation_count":42,"is_preprint":false},{"pmid":"10542032","id":"PMC_10542032","title":"Sequence and initial characterization of the U(L)10 (glycoprotein M) and U(L)11 homologous genes of serotype 1 Marek's Disease Virus.","date":"1999","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/10542032","citation_count":28,"is_preprint":false},{"pmid":"31131438","id":"PMC_31131438","title":"The Ribosomal Protein RPLP0 Mediates PLAAT4-induced Cell Cycle Arrest and Cell Apoptosis.","date":"2019","source":"Cell biochemistry and 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Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/28986221","citation_count":20,"is_preprint":false},{"pmid":"18396911","id":"PMC_18396911","title":"Enhanced secretion of heterologous proteins from yeast by overexpression of ribosomal subunit RPP0.","date":"2008","source":"Biotechnology progress","url":"https://pubmed.ncbi.nlm.nih.gov/18396911","citation_count":16,"is_preprint":false},{"pmid":"35342398","id":"PMC_35342398","title":"miR-4731-5p Enhances Apoptosis and Alleviates Epithelial-Mesenchymal Transition through Targeting RPLP0 in Non-Small-Cell Lung Cancer.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35342398","citation_count":12,"is_preprint":false},{"pmid":"1939187","id":"PMC_1939187","title":"Protein topography of Sulfolobus solfataricus ribosomes by cross-linking with 2-iminothiolane. Sso L12e, Sso L10e, and Sso L11e are neighbors.","date":"1991","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1939187","citation_count":10,"is_preprint":false},{"pmid":"37894825","id":"PMC_37894825","title":"LRP10, PGK1 and RPLP0: Best Reference Genes in Periprostatic Adipose Tissue under Obesity and Prostate Cancer Conditions.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37894825","citation_count":9,"is_preprint":false},{"pmid":"1594456","id":"PMC_1594456","title":"Identification of L10e/L12e ribosomal protein genes in Babesia bovis.","date":"1992","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/1594456","citation_count":9,"is_preprint":false},{"pmid":"9764560","id":"PMC_9764560","title":"Evaluation of restriction fragment length polymorphism analysis of the UL10-UL13 genomic region for rapid identification of human cytomegalovirus strains.","date":"1998","source":"European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/9764560","citation_count":9,"is_preprint":false},{"pmid":"39110356","id":"PMC_39110356","title":"TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.","date":"2024","source":"Apoptosis : an international journal on programmed cell death","url":"https://pubmed.ncbi.nlm.nih.gov/39110356","citation_count":8,"is_preprint":false},{"pmid":"20863866","id":"PMC_20863866","title":"Identification of a peptide sequence targeting mammary vasculature via RPLP0 during lactation.","date":"2010","source":"Peptides","url":"https://pubmed.ncbi.nlm.nih.gov/20863866","citation_count":8,"is_preprint":false},{"pmid":"32668052","id":"PMC_32668052","title":"Phosphorylation of the N-terminal domain of ribosomal P-stalk protein uL10 governs its association with the ribosome.","date":"2020","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/32668052","citation_count":7,"is_preprint":false},{"pmid":"38948092","id":"PMC_38948092","title":"RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation.","date":"2024","source":"World journal of stem cells","url":"https://pubmed.ncbi.nlm.nih.gov/38948092","citation_count":5,"is_preprint":false},{"pmid":"36328276","id":"PMC_36328276","title":"Identification of a novel alternatively spliced isoform of the ribosomal uL10 protein.","date":"2022","source":"Biochimica et biophysica acta. Gene regulatory mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/36328276","citation_count":3,"is_preprint":false},{"pmid":"39383650","id":"PMC_39383650","title":"MicroRNA-450b-5p modulated RPLP0 promotes hepatocellular carcinoma progression via activating JAK/STAT3 pathway.","date":"2024","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39383650","citation_count":3,"is_preprint":false},{"pmid":"31419120","id":"PMC_31419120","title":"Structural and Mutagenesis Studies Evince the Role of the Extended Protuberant Domain of Ribosomal Protein uL10 in Protein Translation.","date":"2019","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31419120","citation_count":3,"is_preprint":false},{"pmid":"17469782","id":"PMC_17469782","title":"Characterization of the full-length cDNA, chromosomal localization, and polymorphism of the porcine RPLP0 gene.","date":"2007","source":"Journal of genetics and genomics = Yi chuan xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/17469782","citation_count":2,"is_preprint":false},{"pmid":"41312719","id":"PMC_41312719","title":"c‑Myc‑regulated RPLP0 via the ROS‑mediated JAK2/STAT3 positive feedback loop facilitates hepatocellular carcinoma malignancy progression.","date":"2025","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41312719","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.03.28.645676","title":"Alternative splicing generates a Ribosomal Protein S24 isoform induced by neuroinflammation and neurodegeneration","date":"2025-04-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.28.645676","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.11.17.624028","title":"Advancing Remote and Low-Resource Healthcare Delivery with Microbiopsy Skin Sample mRNA Housekeeping Gene Stability Analysis Across Various Temperatures","date":"2024-11-18","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.17.624028","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.12.603332","title":"Identification of stable reference genes for quantitative real-time PCR in human fibroblasts from lymph nodes and synovium","date":"2024-07-12","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.12.603332","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17852,"output_tokens":3852,"usd":0.055668,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11560,"output_tokens":4104,"usd":0.0802,"stage2_stop_reason":"end_turn"},"total_usd":0.135868,"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\": 1999,\n      \"finding\": \"Ribosomal protein L10e (uL10/RPLP0) is required for sordarin sensitivity in yeast; mutations in a conserved 10-amino acid region of L10e confer resistance to the eEF2 inhibitor sordarin by reducing sordarin-stabilized eEF2-nucleotide-ribosome complex formation, establishing a functional linkage between L10e and translocation by eEF2.\",\n      \"method\": \"Biochemical and molecular genetic analysis of sordarin-resistant mutants; sequencing of L10e alleles; in vitro eEF2-ribosome-nucleotide complex stabilization assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro biochemical assay combined with mutagenesis identifying causal residues, replicated across multiple alleles\",\n      \"pmids\": [\"9988728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Ricin A chain physically cross-links to ribosomal proteins L9 and L10e (RPLP0) on mammalian ribosomes, identifying L10e as a ribosome-surface component accessible to the toxin; ricin A chain localizes to the endoplasmic reticulum and nucleoli in permeabilized cells.\",\n      \"method\": \"Chemical cross-linking with 125I-labeled ricin A chain on purified mammalian ribosomes; tryptic peptide sequencing; indirect immunofluorescence; competition with excess unlabeled ricin A chain as specificity control\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro cross-linking on purified ribosomes with sequence-level identification of the binding partner and rigorous specificity controls\",\n      \"pmids\": [\"7759553\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1991,\n      \"finding\": \"In the archaebacterium Sulfolobus solfataricus, L10e (uL10) is a near neighbor of L12e (the L7/L12 homolog) in the large ribosomal subunit, forming part of a pentameric (L12e)4–L10e complex that constitutes the factor-binding domain; this organization is conserved across eubacteria, archaea, and eukaryotes.\",\n      \"method\": \"Chemical cross-linking with 2-iminothiolane; two-dimensional diagonal SDS-PAGE; N-terminal sequencing of cross-linked partners\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous in vitro cross-linking and sequencing in a single study on an archaeal ortholog; functional conservation inferred but not directly tested in mammalian cells\",\n      \"pmids\": [\"1939187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Overexpression of yeast ribosomal protein Rpp0 (uL10/RPLP0 ortholog) cures prion determinants [PSI+PS] and [PSI+] in a prion-strain-specific manner, at least partly by modulating chaperone-related promoter activity (SSA4, HSP104).\",\n      \"method\": \"Multicopy yeast genomic library screen; prion curing assays; promoter-reporter assays for chaperone gene expression\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional genetic screen plus reporter assays in yeast ortholog, multiple prion strains tested\",\n      \"pmids\": [\"11923285\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Upon nucleolar stress, the uL10 (RPLP0) protein is released from pre-existing ribosomes and accumulates in the cytoplasm as a ribosome-free pool in mammalian cells, indicating a stress-responsive regulatory role beyond translation.\",\n      \"method\": \"Biochemical fractionation; advanced fluorescence microscopy; FRAP after photoconversion (FRAP-AC) in mammalian cells\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (fractionation + live-cell FRAP-AC) in mammalian cells demonstrating ribosome release under stress\",\n      \"pmids\": [\"28986221\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Phosphorylation within the N-terminal rRNA-binding domain of uL10 (RPLP0) impairs its association with the ribosome; introduction of a negative charge at N-terminal sites reduces ribosome binding, revealing a phosphorylation-dependent regulatory mechanism governing P-stalk assembly and GTPase-associated center activity.\",\n      \"method\": \"Phosphorylation site mapping; mutagenesis introducing negative charge mimics; ribosome association assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with functional ribosome-binding assay in a single study\",\n      \"pmids\": [\"32668052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The extended protuberant (uL10ext) domain of eukaryotic uL10 (RPLP0) contains a conserved 'hinge' region around Phe183 that undergoes conformational rearrangement; substitution of the equivalent yeast residue (F181A) increases polyphenylalanine synthesis ~33% in an in vitro translation assay, demonstrating that hinge motion facilitates binding of translation factors to the GTPase-associated center.\",\n      \"method\": \"NMR structure determination (solution structure of uL10ext domain from Bombyx mori); 15N relaxation analysis; yeast mutant strain construction; in vitro translation assay\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — structure plus mutagenesis plus in vitro functional assay in a single rigorous study\",\n      \"pmids\": [\"31419120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RPLP0 interacts with cathepsin X/Z (CTSX) in gastric cancer cells; knockdown of RPLP0 causes G1 cell cycle arrest and down-regulates CDK2, and affects p21 expression (but not Cyclin E), placing RPLP0 as an anti-apoptotic regulator; CTSX knockdown causes nuclear translocation of RPLP0.\",\n      \"method\": \"Yeast two-hybrid; co-immunoprecipitation; co-localization by laser-scan microscopy; siRNA knockdown; cell cycle analysis; western blotting\",\n      \"journal\": \"Pathology, research and practice\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP confirming interaction, plus knockdown with defined molecular phenotype (CDK2, p21), single lab\",\n      \"pmids\": [\"25433997\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RPLP0 physically interacts with the tumor suppressor PLAAT4; RPLP0 protein levels are suppressed in PLAAT4-expressing cells, and RPLP0 silencing phenocopies PLAAT4 expression (decreased viability, reduced cell-cycle and anti-apoptotic proteins), indicating RPLP0 mediates PLAAT4-induced cell cycle arrest and apoptosis.\",\n      \"method\": \"Yeast two-hybrid screening; co-immunoprecipitation; co-localization; siRNA knockdown; cell viability assays; western blotting\",\n      \"journal\": \"Cell biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus co-IP confirming interaction, plus knockdown phenocopy, single lab\",\n      \"pmids\": [\"31131438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"RPLP0 functions as a cell-surface receptor on mammary endothelial cells during lactation, mediating binding and internalization of the MG1 homing peptide (CLHQHNQMC) identified by in vivo phage display.\",\n      \"method\": \"In vivo phage display biopanning; peptide affinity pull-down assay; immunoblotting; in vitro endothelial cell internalization assay; competitive inhibition with synthetic peptide\",\n      \"journal\": \"Peptides\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pull-down plus functional internalization assay with competitive inhibition control; surface localization of a classically cytoplasmic protein is unusual and warrants caution\",\n      \"pmids\": [\"20863866\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"An alternatively spliced isoform of uL10 (named uL10β) is stably expressed in mammalian cells, localizes predominantly to the nucleus, can associate with 60S and 80S ribosomal particles, and undergoes re-localization to mitochondria upon ER stress, suggesting a specialized stress-related function.\",\n      \"method\": \"RT-PCR/sequencing of isoform; subcellular fractionation; fluorescence microscopy; ribosome sedimentation assays; ER stress induction experiments\",\n      \"journal\": \"Biochimica et biophysica acta. Gene regulatory mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (fractionation, imaging, sucrose gradient) in a single study characterizing a novel isoform\",\n      \"pmids\": [\"36328276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Overexpression of yeast RPP0 (RPLP0 ortholog) enhances secretion of heterologous proteins; the effect does not appear to involve ribosome function directly, but instead RPP0 overexpression prevents upregulation of the yeast plasma membrane H+-ATPase gene PMA1, thereby limiting medium acidification.\",\n      \"method\": \"Gene overexpression in S. cerevisiae; secretion yield assays; gene expression analysis of PMA1\",\n      \"journal\": \"Biotechnology progress\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect mechanistic inference from expression data for PMA1 link, no direct biochemical confirmation\",\n      \"pmids\": [\"18396911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPLP0 knockdown activates apoptosis signaling in human umbilical vein endothelial cells and enhances endothelial permeability; TNF-α treatment combined with RPLP0 knockdown synergistically increases these effects, placing RPLP0 as an anti-apoptotic factor in endothelial cells relevant to high-altitude pulmonary edema.\",\n      \"method\": \"In vivo HAPE rat model validation; siRNA knockdown in HUVECs; apoptosis assays; permeability assays\",\n      \"journal\": \"Apoptosis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional knockdown with defined cellular readout but no detailed molecular pathway dissection; single study\",\n      \"pmids\": [\"39110356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPLP0 promotes HCC cell proliferation, invasion, and migration partly through activation of the JAK/STAT3 pathway; miR-450b-5p directly targets the RPLP0 3'UTR (validated by luciferase reporter assay) to downregulate RPLP0 and suppress this pathway.\",\n      \"method\": \"Luciferase reporter assay; siRNA knockdown; xenograft tumor assay; western blotting for JAK/STAT3 pathway components\",\n      \"journal\": \"Translational oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, pathway association by knockdown without biochemical reconstitution of RPLP0-JAK/STAT3 link\",\n      \"pmids\": [\"39383650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"c-Myc directly binds the RPLP0 promoter and activates its transcription; RPLP0 in turn activates the JAK2/STAT3 pathway via ROS suppression, which upregulates c-Myc, forming a positive feedback loop driving HCC progression.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP); dual luciferase promoter assay; siRNA knockdown; ROS measurement; western blotting for JAK2/STAT3/c-Myc\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus luciferase assay establish direct transcriptional regulation; knockdown experiments with pathway readouts; single lab\",\n      \"pmids\": [\"41312719\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPLP0 (uL10) is the core scaffold of the ribosomal P-stalk in the GTPase-associated center (GAC), anchoring P1/P2 heterodimers to the 60S subunit via its N-terminal rRNA-binding domain; N-terminal phosphorylation of uL10 negatively regulates its ribosome association, providing a regulatory switch for GAC activity; a conserved 'hinge' motion in its extended protuberant domain facilitates sequential binding of translational GTPases (eEF2, eRF1) required for translocation and termination; under nucleolar stress, uL10 is released from ribosomes as a free cytoplasmic pool; an alternatively spliced isoform (uL10β) localizes primarily to the nucleus and redistributes to mitochondria upon ER stress; beyond translation, RPLP0 interacts with cathepsin X/Z and PLAAT4 to modulate cell cycle progression and apoptosis (via CDK2/p21), is transcriptionally activated by c-Myc and reciprocally sustains a JAK2/STAT3/c-Myc feedback loop in cancer cells, and was identified as a cell-surface receptor on mammary endothelial cells mediating peptide internalization during lactation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPLP0 (uL10) is the core scaffold of the ribosomal P-stalk in the GTPase-associated center (GAC) of the large subunit, the platform that recruits translational GTPases for elongation and termination [#0, #2]. In the archaeal and conserved organization, uL10 nucleates a pentameric (P-protein)4–uL10 factor-binding complex adjacent to the L7/L12 (P1/P2) homologs [#2], and it sits at a ribosome-surface position accessible to exogenous ligands, as shown by direct cross-linking of ricin A chain to L10e on mammalian ribosomes [#1]. Functionally, uL10 is coupled to eEF2-driven translocation: mutations in a conserved region confer resistance to the eEF2 inhibitor sordarin by destabilizing the eEF2–nucleotide–ribosome complex [#0], and a conserved 'hinge' around Phe183 in the extended protuberant (uL10ext) domain undergoes conformational rearrangement that gates factor binding, since hinge mutation increases in vitro polyphenylalanine synthesis [#6]. P-stalk assembly is regulated by phosphorylation within the N-terminal rRNA-binding domain, which introduces negative charge that impairs ribosome association and thereby tunes GAC activity [#5]. Beyond steady-state translation, uL10 is released from pre-existing ribosomes into a free cytoplasmic pool under nucleolar stress [#4], and an alternatively spliced isoform (uL10β) localizes predominantly to the nucleus, associates with 60S/80S particles, and redistributes to mitochondria upon ER stress [#10]. Extra-ribosomal activities have also been reported: RPLP0 binds cathepsin X/Z (CTSX) and the tumor suppressor PLAAT4 to influence G1 progression and apoptosis through CDK2/p21 [#7, #8], and c-Myc directly activates RPLP0 transcription while RPLP0 sustains a JAK2/STAT3/c-Myc feedback loop in hepatocellular carcinoma [#14].\",\n  \"teleology\": [\n    {\n      \"year\": 1991,\n      \"claim\": \"Establishing where uL10 sits in the ribosome was the first step in defining its function; cross-linking placed it as a near neighbor of the L12e (P1/P2) proteins within the conserved factor-binding domain.\",\n      \"evidence\": \"2-iminothiolane cross-linking and N-terminal sequencing of the (L12e)4–L10e complex in archaeal ribosomes\",\n      \"pmids\": [\"1939187\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Conservation to mammalian ribosomes inferred but not directly tested here\",\n        \"Does not establish how uL10 engages translational GTPases functionally\"\n      ]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Cross-linking of ricin A chain confirmed L10e/RPLP0 is a surface-exposed component of mammalian ribosomes, anchoring the archaeal organization in the mammalian context.\",\n      \"evidence\": \"Chemical cross-linking of 125I-ricin A chain on purified mammalian ribosomes with tryptic peptide sequencing and competition controls\",\n      \"pmids\": [\"7759553\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not define the catalytic or factor-recruitment role of L10e\",\n        \"Functional consequence of the ricin-uL10 proximity not established\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Linking uL10 to translocation: sordarin-resistance mutations showed L10e is functionally coupled to eEF2-mediated elongation, not merely structural.\",\n      \"evidence\": \"Sordarin-resistant L10e allele sequencing and in vitro eEF2–ribosome–nucleotide complex stabilization assays in yeast\",\n      \"pmids\": [\"9988728\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not resolve the structural mechanism of factor engagement\",\n        \"Limited to eEF2; other GTPases not addressed in this study\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"A yeast genetic screen revealed an unexpected link between the uL10 ortholog and prion propagation via chaperone gene expression, hinting at functions beyond translation.\",\n      \"evidence\": \"Multicopy genomic library screen, prion-curing assays, and chaperone promoter-reporter assays in yeast\",\n      \"pmids\": [\"11923285\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism connecting Rpp0 overexpression to chaperone promoters unresolved\",\n        \"Relevance to mammalian RPLP0 untested\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"RPLP0 was identified at the cell surface acting as a receptor for a homing peptide, an unusual extra-ribosomal localization.\",\n      \"evidence\": \"In vivo phage display, peptide affinity pull-down, and endothelial internalization assay with competitive inhibition\",\n      \"pmids\": [\"20863866\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Surface display of a classically cytoplasmic protein not mechanistically explained\",\n        \"No structural basis for peptide recognition\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identification of RPLP0–cathepsin X/Z interaction and a CDK2/p21-linked cell-cycle phenotype framed RPLP0 as an anti-apoptotic, cell-cycle regulator in cancer cells.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal co-IP, co-localization, siRNA knockdown, and cell cycle analysis in gastric cancer cells\",\n      \"pmids\": [\"25433997\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the cell-cycle effect is ribosome-dependent or extra-ribosomal unclear\",\n        \"Direct biochemical mechanism linking RPLP0 to CDK2/p21 not defined\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrating stress-induced release answered whether uL10 is a static subunit: under nucleolar stress it exits ribosomes to form a free cytoplasmic pool.\",\n      \"evidence\": \"Biochemical fractionation and FRAP after photoconversion (FRAP-AC) in mammalian cells\",\n      \"pmids\": [\"28986221\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Function of the free cytoplasmic pool not established\",\n        \"Trigger linking nucleolar stress to release mechanistically undefined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Two studies refined uL10 mechanism: a conserved Phe183 'hinge' in the uL10ext domain gates translation-factor binding, and a PLAAT4 interaction tied RPLP0 to tumor-suppressor-induced apoptosis.\",\n      \"evidence\": \"NMR solution structure with 15N relaxation plus yeast F181A mutant and in vitro translation; and yeast two-hybrid/co-IP/knockdown phenocopy for PLAAT4\",\n      \"pmids\": [\"31419120\", \"31131438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How hinge dynamics coordinate sequential eEF2/eRF1 binding not directly resolved\",\n        \"PLAAT4–RPLP0 mechanism (single-lab) lacks reciprocal in vivo validation\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying N-terminal phosphorylation as a switch showed P-stalk assembly is actively regulated: negative charge in the rRNA-binding domain impairs ribosome association.\",\n      \"evidence\": \"Phosphosite mapping, phosphomimetic mutagenesis, and ribosome association assays\",\n      \"pmids\": [\"32668052\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Kinase responsible not identified\",\n        \"Physiological conditions driving phosphorylation undefined\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Characterization of the uL10β splice isoform revealed a nuclear-localizing, ribosome-associating variant that relocates to mitochondria under ER stress, expanding the functional repertoire.\",\n      \"evidence\": \"Isoform RT-PCR/sequencing, subcellular fractionation, imaging, and ribosome sedimentation with ER stress induction\",\n      \"pmids\": [\"36328276\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Function of mitochondrial relocalization unknown\",\n        \"Whether uL10β supports translation distinct from canonical uL10 untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Integration into a transcriptional circuit: c-Myc directly activates RPLP0, which sustains JAK2/STAT3 via ROS suppression to reinforce c-Myc, defining a feedback loop in HCC; related work tied RPLP0 to endothelial apoptosis and miR-450b-5p regulation.\",\n      \"evidence\": \"ChIP and dual-luciferase promoter assays with ROS measurement and pathway westerns; plus knockdown studies in HUVECs and HCC with luciferase 3'UTR targeting\",\n      \"pmids\": [\"41312719\", \"39110356\", \"39383650\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical link between RPLP0 and JAK2/STAT3 not reconstituted\",\n        \"Whether the cancer roles depend on ribosomal vs extra-ribosomal RPLP0 unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPLP0's canonical P-stalk function mechanistically connects to its reported extra-ribosomal roles in cell-cycle control, apoptosis, and oncogenic signaling remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical bridge between the free/nuclear pool and signaling functions\",\n        \"Kinases, recruitment factors, and stress sensors governing relocalization unidentified\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 1]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [1, 2, 10]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [7, 10]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-72766\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [4, 10]}\n    ],\n    \"complexes\": [\n      \"ribosomal P-stalk / GTPase-associated center\"\n    ],\n    \"partners\": [\n      \"RPLP1\",\n      \"RPLP2\",\n      \"eEF2\",\n      \"CTSZ\",\n      \"PLAAT4\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}