Affinage

RPL5

Large ribosomal subunit protein uL18 · UniProt P46777

Length
297 aa
Mass
34.4 kDa
Annotated
2026-06-10
84 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL5/uL18 is a structural protein of the large (60S) ribosomal subunit that doubles as a sensor of ribosome biogenesis stress, coupling assembly status to the p53 tumor suppressor pathway (PMID:23478443, PMID:29143558). Its incorporation into nascent particles requires dedicated assembly factors that co-recruit RPL5, RPL11 and 5S rRNA into preribosomes, a step whose failure blocks pre-rRNA processing and nuclear export (PMID:17938242), while nuclear delivery of RPL5 depends on the import adaptor HEATR3 (PMID:35213692). When ribosome assembly is perturbed — by loss of assembly factors, disruption of 40S subunit formation, or pharmacological nucleolar stress — extra-ribosomal RPL5 accumulates as part of the 5S RNP and directly binds MDM2 to inhibit its E3 ligase activity, stabilizing and activating p53 (PMID:29143558, PMID:35719981, PMID:31986150). This MDM2-binding pool is set by multiple upstream regulators: SPIN1 and increased mature rRNA (driven by hMTR4) sequester RPL5 in the nucleolus away from MDM2 (PMID:29547122, PMID:40652043); WDR74 and DDX24 lower RPL5 protein levels by promoting its degradation (PMID:32005977, PMID:35864588); and transcription factors MeCP2 and ZBTB7A repress, while PRDM16 enhances, RPL5 expression, each tuning p53 output and cell proliferation in cancer (PMID:32483207, PMID:41910727, PMID:38896079). Beyond the MDM2–p53 axis, RPL5 acts as a co-regulator of c-Myc degradation through direct binding to RBM10 (PMID:38032932), and is recruited to DNA double-strand breaks in a PARP- and p53-dependent manner where it interacts with poly(ADP-ribose), Ku70 and histone H2A to influence repair pathway choice (PMID:39416207). Through its core role in ribosome content and translational capacity, RPL5 limits cell cycle progression and organismal growth independently of p53 (PMID:24061479, PMID:24558476). RPL5 haploinsufficiency causes the ribosomopathy Diamond-Blackfan anemia, driving p53-mediated ferroptosis of erythroid progenitors and apoptosis in specific lineages such as chondrocytes (PMID:41951665, PMID:34587661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2007 High

    Established how RPL5 is delivered into the ribosome assembly pathway, showing it is co-recruited with RPL11 and 5S rRNA by dedicated assembly factors and that this step gates pre-rRNA processing and subunit export.

    Evidence In vitro binding assays, co-IP, and genetic depletion with pre-rRNA processing readouts in the yeast ortholog system

    PMID:17938242

    Open questions at the time
    • Does not address how the extra-ribosomal pool is generated in human cells
    • Human orthologs of Rpf2/Rrs1 not directly tested here
  2. 2013 High

    Defined the extra-ribosomal function of RPL5 as a necessary component of an MDM2-containing complex that stabilizes p53, separating this checkpoint role from RPL5's ribosomal role.

    Evidence Reciprocal co-IP, knockdown, and p53 stabilization/senescence assays linking SRSF1 to the RPL5-MDM2 complex

    PMID:23478443

    Open questions at the time
    • Stoichiometry of the 5S RNP–MDM2 complex not resolved
    • Direct binding interface of RPL5 on MDM2 not mapped here
  3. 2013 High

    Showed that RPL5 controls normal proliferation through translational capacity rather than a p53 checkpoint, by limiting ribosome content and cyclin translation.

    Evidence siRNA knockdown with cell cycle analysis, ribosome profiling and cyclin quantification in primary fibroblasts

    PMID:24061479

    Open questions at the time
    • Which specific transcripts are most sensitive to reduced ribosome content not defined
    • Relationship between this role and the MDM2-p53 pool not integrated
  4. 2014 Medium

    Demonstrated p53-independent consequences of RPL5 loss, with haploinsufficient ES cells showing G2/M delay and growth defects not rescued by p53 knockdown.

    Evidence Gene-trap murine ES cell lines with polysome profiling, cell cycle analysis and p53 knockdown rescue

    PMID:24558476

    Open questions at the time
    • Molecular basis of the p53-independent G2/M delay unknown
    • Distinct from RPS19 phenotype but shared/divergent mechanisms not fully resolved
  5. 2017 Medium

    Placed RPL5 downstream of broad ribosome biogenesis perturbation, showing HEATR1 ablation activates the RPL5/RPL11-MDM2-p53 checkpoint.

    Evidence siRNA knockdown of HEATR1 with RPL5/RPL11 double-knockdown epistasis and p53 activation/cell cycle readouts

    PMID:29143558

    Open questions at the time
    • Does not establish direct biochemical link between HEATR1 loss and free RPL5 generation
    • Single-lab epistasis
  6. 2018 High

    Identified nucleolar sequestration as a regulatory mechanism: SPIN1 binds RPL5 and retains it in the nucleolus, restricting the MDM2-binding pool and inactivating p53.

    Evidence Reciprocal co-IP, nucleolar fractionation, and rescue showing RPL5 requirement for p53 activation upon SPIN1 depletion

    PMID:29547122

    Open questions at the time
    • Structural basis of SPIN1-RPL5 binding not defined
    • Whether SPIN1 acts on 5S RNP or free RPL5 unclear
  7. 2020 Medium

    Showed transcriptional control of the RPL5 set point: MeCP2 represses RPL5 transcription to lower the MDM2-inhibitory pool and promote p53 degradation in breast cancer.

    Evidence ChIP for promoter binding, RPL5-MDM2 co-IP, knockdown/overexpression with proliferation assays

    PMID:32483207

    Open questions at the time
    • Direct vs indirect promoter effects not fully separated
    • Single cancer context
  8. 2020 Medium

    Established post-translational control of RPL5 abundance, with WDR74 reducing RPL5 protein to insulate MDM2 and permit p53 degradation in melanoma.

    Evidence Co-IP, protein stability assays, WDR74 gain/loss-of-function, and xenograft

    PMID:32005977

    Open questions at the time
    • Whether WDR74 acts via a defined E3 ligase not shown
    • Direct vs indirect effect on RPL5 stability unresolved
  9. 2020 Medium

    Clarified the source of extra-ribosomal RPL5, showing that disrupting 40S assembly generates free uL18 during 60S assembly rather than from turnover of mature subunits.

    Evidence Sucrose gradient sedimentation and fractionation after small-subunit RP gene repression in yeast

    PMID:31986150

    Open questions at the time
    • Mechanism coupling 40S disruption to free 60S-component release not defined
    • Human relevance inferred from yeast
  10. 2021 Medium

    Linked RPL5 haploinsufficiency to lineage-specific p53-mediated apoptosis, accounting for skeletal abnormalities in Diamond-Blackfan anemia.

    Evidence iPSC-derived chondrocyte vs osteoblast differentiation from DBA patient cells, MDM2 phosphorylation and apoptosis readouts

    PMID:34587661

    Open questions at the time
    • Basis for chondrocyte- vs osteoblast-selective sensitivity unknown
    • Single-lab patient-derived model
  11. 2022 High

    Defined the nuclear import requirement for RPL5, identifying HEATR3 as an adaptor whose loss impairs nuclear uL18 accumulation, ribosome assembly, and produces DBA-like phenotypes.

    Evidence Patient-derived fibroblasts, HEATR3 depletion/variant expression across human and yeast systems, fractionation and pre-rRNA processing assays

    PMID:35213692

    Open questions at the time
    • Whether HEATR3 import defects feed into the p53 checkpoint not directly tested
    • Import mechanism at molecular level not resolved
  12. 2022 Medium

    Extended the regulatory network to RPL5 protein turnover by DDX24, which promotes RPL5 ubiquitination and degradation to drive NSCLC migration/invasion.

    Evidence Co-IP/MS, protein stability and ubiquitination assays, knockdown/overexpression with migration readouts

    PMID:35864588

    Open questions at the time
    • E3 ligase mediating DDX24-dependent RPL5 degradation not identified
    • Connection to p53 output not directly shown
  13. 2022 Medium

    Demonstrated pharmacological induction of the RPL5-MDM2-p53 checkpoint, with PARP inhibition causing nucleolar stress that enhances RPL5-MDM2 binding.

    Evidence Co-IP of RPL5-MDM2, RPL5/RPL11 knockdown epistasis, pre-rRNA inhibition and p53 reporter assays

    PMID:35719981

    Open questions at the time
    • Direct effect of olaparib on rRNA synthesis machinery not mechanistically detailed
    • Single-lab
  14. 2023 High

    Identified an MDM2-independent effector role: RPL5 directly binds RBM10 to enhance RBM10-driven c-Myc ubiquitin-dependent degradation, with a cancer mutation in RBM10 abolishing both binding and c-Myc control.

    Evidence Reciprocal co-IP, ubiquitination assays, and RBM10 mutational interface analysis with proliferation readouts

    PMID:38032932

    Open questions at the time
    • Whether free RPL5 or ribosomal RPL5 engages RBM10 unclear
    • Structural detail of RPL5-RBM10 interface not resolved
  15. 2024 Medium

    Added a transcriptional activator to the network: PRDM16 binds and enhances the RPL5 promoter and physically associates with RPL5 to suppress p53 and protect retinal ganglion cells via downstream FCGR2B/MAPK/NLRP3 signaling.

    Evidence ChIP, co-IP, PRDM16 overexpression and RGC-specific deletion with pathway assays

    PMID:41910727

    Open questions at the time
    • Direct vs indirect contribution of the PRDM16-RPL5 physical interaction not separated
    • Single context
  16. 2024 Medium

    Implicated RPL5 in DNA double-strand break repair, showing PARP- and p53-dependent recruitment to breaks and interactions with PAR, Ku70 and H2A that bias repair pathway choice.

    Evidence Laser-microirradiation recruitment, co-IP with repair factors, DSB repair reporters and RAD51 foci (preprint)

    PMID:39416207

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Whether DSB role uses extra-ribosomal or 5S-RNP-bound RPL5 unknown
    • Mechanism linking RPL5 to RAD51 reduction not defined
  17. 2024 Medium

    Confirmed in vivo that biogenesis failure drives nucleoplasmic RPL5/RPL11 translocation and p53-dependent cell death, while also revealing p53-independent functional defects.

    Evidence Conditional Nat10 knockout mouse, RPL5/RPL11 immunolocalization and p53 deletion epistasis (preprint)

    PMID:bio_10.1101_2024.09.25.614959

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Nature of p53-independent defects not molecularly defined
  18. 2025 High

    Resolved how mature rRNA tunes the RPL5 checkpoint, with hMTR4 promoting rRNA processing to sequester RPL5 in the nucleolus and reduce the MDM2-binding pool.

    Evidence hMTR4 gain/loss-of-function, fractionation, RPL5-MDM2 co-IP, and RPL5 knockdown epistasis on p53

    PMID:40652043

    Open questions at the time
    • Quantitative relationship between rRNA levels and free RPL5 not modeled
    • Whether sequestration is via 5S RNP or free protein unclear
  19. 2025 High

    Defined the in vivo mechanism of RPL5-driven Diamond-Blackfan anemia as p53-mediated ferroptosis of erythroid progenitors, mechanistically distinct from RPS19-driven apoptosis.

    Evidence In vivo mouse haploinsufficiency models with HSPC flow cytometry and ferroptosis-vs-apoptosis pathway dissection

    PMID:41951665

    Open questions at the time
    • Why erythroid progenitors specifically undergo ferroptosis not fully explained
    • Link between p53 activation and ferroptosis effectors not detailed
  20. 2025 Medium

    Showed a disease-associated RPL5 point mutation alters ribosome output, with RPL5-I60V conferring increased translational activity and proliferation in T-ALL.

    Evidence CRISPR knock-in of RPL5-I60V in Jurkat cells with ribosome biogenesis, global translation, proliferation and drug-sensitivity assays

    PMID:41177179

    Open questions at the time
    • Structural basis for hyperactive translation not defined
    • Whether the mutation affects the MDM2 checkpoint untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which molecular form of RPL5 (free protein versus the 5S RNP) engages each of its diverse partners (MDM2, RBM10, DSB repair factors) and how cells partition RPL5 among ribosome assembly, checkpoint signaling, and these extra-ribosomal roles.
  • Form-specific binding partners not mapped
  • Quantitative flux of RPL5 between pools unmeasured
  • Integration of MDM2-p53, c-Myc, and DSB roles not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 1
Localization
GO:0005730 nucleolus 3 GO:0005840 ribosome 3 GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
DDX24HEATR3KU70MDM2PRDM16RBM10SPIN1WDR74
Complex memberships
5S ribonucleoprotein particle60S ribosomal subunitMDM2-ribosomal protein complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Assembly factors Rpf2 and Rrs1 are required to recruit ribosomal proteins rpL5 (yeast ortholog) and rpL11, along with 5S rRNA, into nascent 90S preribosomal particles. In the absence of this recruitment, 27SB pre-rRNA processing is blocked and abortive 66S pre-rRNPs are prematurely released from the nucleolus to the nucleoplasm and cannot be exported to the cytoplasm. Direct protein-protein interactions between Rpf2, Rrs1, rpL5, and rpL11 were confirmed by in vitro binding assays. In vitro binding assays, co-immunoprecipitation, sucrose gradient sedimentation, genetic depletion with pre-rRNA processing readout Genes & development High 17938242
2013 RPL5 is a necessary component of an MDM2/ribosomal protein complex (separate from the ribosome) that functions in a p53-dependent ribosomal-stress checkpoint pathway. SRSF1 overexpression stabilizes p53 by abrogating MDM2-dependent proteasomal degradation through this RPL5-containing MDM2 complex, linking the spliceosomal and ribosomal components in monitoring cell physiology independently of their canonical roles. Co-immunoprecipitation, knockdown experiments, p53 stabilization assays, cell proliferation and senescence assays Molecular cell High 23478443
2013 Loss of RPL5 (or RPL11) in primary human lung fibroblasts does not induce cell cycle arrest but suppresses cell cycle progression by reducing ribosome content and translational capacity, which in turn suppresses the accumulation of cyclins at the translational level. This is distinct from other tumor suppressors and demonstrates that RPL5/RPL11's role in normal cell proliferation is relied upon in lieu of a p53-dependent cell cycle checkpoint. siRNA knockdown, cell cycle analysis (FACS), ribosome profiling, cyclin protein quantification, primary fibroblast culture Molecular and cellular biology High 24061479
2018 SPIN1 (Spindlin 1) binds RPL5/uL18 and sequesters it in the nucleolus, preventing RPL5 from interacting with MDM2. This alleviates RPL5-mediated inhibition of MDM2 ubiquitin ligase activity toward p53, thereby inactivating p53. SPIN1 deficiency increases ribosome-free RPL5 and RPL11, which are both required for SPIN1 depletion-induced p53 activation. Co-immunoprecipitation, subcellular fractionation/nucleolar localization experiments, knockdown with p53 activation readout, clonogenic and apoptosis assays eLife High 29547122
2020 MeCP2 represses RPL5 (and RPL11) transcription by binding to their promoter regions. Reduced RPL5 consequently decreases its direct binding to MDM2, relieving MDM2 inhibition and promoting ubiquitination-mediated P53 degradation, thereby facilitating breast cancer cell proliferation. ChIP assay (MeCP2 binding to RPL5 promoter), co-immunoprecipitation (RPL5-MDM2), siRNA knockdown, overexpression, proliferation and cell cycle assays Oncogenesis Medium 32483207
2017 Perturbation of ribosome biogenesis by HEATR1 ablation activates the RPL5/RPL11-MDM2-p53 ribosome biogenesis stress checkpoint pathway, leading to p53-dependent cell cycle arrest. Depletion of HEATR1 caused disruption of nucleolar structure and RPL5/RPL11-dependent stabilization and activation of p53. siRNA knockdown of HEATR1, p53 activation assays, cell cycle analysis, RPL5/RPL11 knockdown as epistasis control Cell cycle Medium 29143558
2022 HEATR3 synchronizes the nuclear import of RPL5/uL18 (and RPL11/uL5). HEATR3 variants or depletion impairs nuclear accumulation of uL18 (demonstrated in patient-derived fibroblasts and cell lines), disrupts pre-rRNA processing and ribosomal subunit formation, and causes DBA-like phenotypes including abnormal erythrocyte maturation and proliferation defects. Patient-derived fibroblast analysis, HEATR3 knockdown/variant expression in cell lines and yeast models, subcellular fractionation for nuclear uL18 accumulation, pre-rRNA processing assays, hematopoietic progenitor differentiation assays Blood High 35213692
2020 WDR74 modulates RPL5 protein levels and consequently regulates MDM2-mediated ubiquitination and degradation of p53. WDR74 overexpression reduces RPL5 protein levels, thereby insulating MDM2 from RPL5 inhibition and allowing p53 degradation, promoting melanoma proliferation and metastasis. Co-immunoprecipitation, protein stability assays, gain/loss-of-function (WDR74), Western blot for RPL5/MDM2/p53 levels, in vivo xenograft Oncogene Medium 32005977
2022 Olaparib (PARP inhibitor) triggers nucleolar stress by inhibiting pre-rRNA biosynthesis, resulting in enhanced interaction between RPL5 and RPL11 with MDM2, thereby stabilizing and activating p53. Knockdown of RPL5 and RPL11 prevents Olaparib-induced p53 activation. Co-immunoprecipitation (RPL5-MDM2 interaction), siRNA knockdown of RPL5/RPL11, pre-rRNA synthesis inhibition assays, p53 reporter assays Frontiers in oncology Medium 35719981
2023 RNA-binding motif protein 10 (RBM10) directly binds RPL5/uL18 and RPL11/uL5, and this interaction boosts RBM10's ability to promote c-Myc ubiquitin-dependent degradation. Cancer-derived mutant RBM10-I316F fails to bind uL18 and uL5 and cannot inactivate c-Myc, demonstrating that RPL5 functions as a co-regulator of c-Myc degradation through its interaction with RBM10. Co-immunoprecipitation, ubiquitination assays, RBM10 mutant analysis, cell growth and proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 38032932
2022 DDX24 interacts with RPL5 and promotes its ubiquitination and proteasomal degradation, thereby destabilizing RPL5 protein and promoting NSCLC cell migration and invasion. Co-immunoprecipitation followed by mass spectrometry, protein stability assays, ubiquitination assays, siRNA knockdown and overexpression with migration/invasion readouts Cancer medicine Medium 35864588
2025 hMTR4 promotes rRNA processing in an RNA helicase-dependent manner, increasing mature rRNA that sequesters RPL5 in the nucleolus, thereby reducing the pool of RPL5 available to bind MDM2 in the nucleoplasm, consequently promoting MDM2-mediated p53 degradation. Silencing RPL5 blocked the effect of hMTR4 knockdown in upregulating p53, and hMTR4 overexpression abrogated RPL5-stimulated p53 activity. Gain/loss-of-function of hMTR4, subcellular fractionation, Co-immunoprecipitation (RPL5-MDM2), rRNA processing assays, p53 ubiquitination and protein level assays, epistasis by RPL5 knockdown Cell death and differentiation High 40652043
2020 Disruption of 40S ribosomal assembly (by repression of small subunit ribosomal protein genes) paradoxically causes accumulation of extra-ribosomal RPL5/uL18, and this extra-ribosomal uL18 is formed during 60S assembly rather than during degradation of mature cytoplasmic 60S subunits. The extent of uL18 accumulation varies depending on which 40S ribosomal protein is repressed. Sucrose gradient sedimentation, ribosomal protein gene repression (yeast model), fractionation to distinguish ribosomal vs. extra-ribosomal uL18 PloS one Medium 31986150
2014 In murine embryonic stem cells haploinsufficient for Rpl5, there is a significant delay in G2/M cell cycle phase that is not rescued by p53 knockdown, and a more pronounced growth defect compared to Rps19 haploinsufficient cells. Rpl5 mutant ES cells showed polysome defects but no significant increase in p53 protein expression (unlike Rps19 mutants), indicating p53-independent cell cycle and growth effects. Gene trap murine ES cell lines, polysome profiling, cell cycle analysis (FACS), p53 knockdown rescue experiments, embryoid body differentiation assays PloS one Medium 24558476
2021 RPL5 haploinsufficiency specifically induces p53-mediated apoptosis in chondrocytes (but not osteoblasts) through MDM2 inhibition. Phosphorylation of MDM2 was significantly decreased in RPL5 haploinsufficient chondrocytes, and pro-apoptotic genes BAX and CASP9 were upregulated, providing a mechanism for skeletal physical abnormalities in DBA patients. iPSC-derived chondrocyte and osteoblast differentiation from DBA patient cells, Western blot for MDM2 phosphorylation and p53 targets, apoptosis assays Pathology international Medium 34587661
2024 RPL5 and RPS19 are recruited to DNA double-strand break (DSB) sites in a poly(ADP-ribose) polymerase (PARP) activity-dependent manner, interact noncovalently with poly(ADP-ribose) chains, and interact with Ku70 and histone H2A. RPL5 knockdown increases end-joining DSB repair pathways and reduces RAD51 levels. RPL5's recruitment to DSBs requires p53, distinguishing its DSB repair role from that of RPS19. ChIP/laser-microirradiation DSB recruitment assays, co-immunoprecipitation (RPL5-Ku70, RPL5-H2A, RPL5-PAR), DSB repair pathway reporter assays, RAD51 foci counting, knockdown experiments bioRxivpreprint Medium 39416207
2025 RPL5 haploinsufficiency causes hematopoietic stem and progenitor cell (HSPC) accumulation and prenatal lethality via p53-mediated ferroptosis of mature erythroid progenitors in fetal hematopoiesis, which is mechanistically distinct from RPS19 haploinsufficiency (which causes HSPC depletion via p53-dependent apoptosis). In vivo mouse models of RPL5 and RPS19 haploinsufficiency, HSPC flow cytometry, cell death pathway analysis (ferroptosis vs. apoptosis markers), p53 pathway activation assays Nature communications High 41951665
2004 RpL5 in Drosophila is haplo-insufficient; heterozygous RpL5 mutations cause classic Minute phenotypes (small bristles, delayed development) and result in abnormally large wings due to increased cell size, demonstrating that RpL5 is limiting for growth control and translational regulation of organ size. Genetic screen, point mutation identification, heterozygous mutant phenotype analysis, wing size and cell size measurement Genetics Medium 15520262
2025 The RPL5-I60V mutation (found in T-ALL) causes both quantitative and qualitative alterations in large ribosomal subunit production. Ribosomes containing the mutant RPL5-I60V exhibit intrinsically increased protein synthesis activity, correlating with enhanced cellular proliferation, and confer increased sensitivity to most translation-targeting compounds (except hygromycin B). CRISPR-Cas9 knock-in of RPL5-I60V in Jurkat cells, ribosome biogenesis assays, global translation measurement, proliferation assays, drug sensitivity panel Biochemical pharmacology Medium 41177179
2024 Inhibition of ribosome biogenesis by Nat10 deletion causes translocation of RPL5 and RPL11 into acinar cell nucleoplasm, which triggers p53-dependent cell death. Deletion of p53 rescues acinar cells from apoptosis but not from morphological/functional abnormalities, demonstrating that nucleoplasmic RPL5/RPL11 translocation activates p53-dependent and p53-independent consequences of ribosome biogenesis failure. Conditional Nat10 knockout mouse model, immunolocalization of RPL5/RPL11, p53 deletion epistasis, histology and functional assays bioRxivpreprint Medium bio_10.1101_2024.09.25.614959
2024 PRDM16 binds to the RPL5 promoter and enhances RPL5 transcription. Additionally, PRDM16 physically associates with RPL5 (co-immunoprecipitation). This PRDM16-mediated enrichment of RPL5 suppresses p53 signaling, leading to upregulation of FCGR2B, which inhibits MAPK (p38 and JNK) signaling and NLRP3/IL-1β inflammasome assembly, protecting retinal ganglion cells from ischemia-reperfusion injury. ChIP assay (PRDM16 binding to RPL5 promoter), co-immunoprecipitation (PRDM16-RPL5), PRDM16 overexpression/RGC-specific deletion, p53 and downstream pathway assays Cellular and molecular life sciences Medium 41910727
2024 ZBTB7A represses RPL5 transcription in pancreatic cancer cells. RPL5 overexpression enhances binding between RPL5 and MDM2 (strengthened by ER stress via PERK-dependent eIF2α phosphorylation), suppressing MDM2-mediated ubiquitination and degradation of P53, and establishing a positive feedback loop where p53 augmentation intensifies ER stress which further enhances RPL5-MDM2 binding. Co-immunoprecipitation (RPL5-MDM2), ZBTB7A knockdown/overexpression, RPL5 overexpression, p53 ubiquitination assays, ER stress marker quantification, xenograft mouse model Molecular carcinogenesis Medium 38896079

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nature genetics 336 23263491
1999 The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18. Immunity 279 10591185
2007 Assembly factors Rpf2 and Rrs1 recruit 5S rRNA and ribosomal proteins rpL5 and rpL11 into nascent ribosomes. Genes & development 167 17938242
2007 The human cytomegalovirus MHC class I homolog UL18 inhibits LIR-1+ but activates LIR-1- NK cells. Journal of immunology (Baltimore, Md. : 1950) 115 17372005
2008 Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes and immunity 106 18650830
2017 The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types. Oncotarget 102 28147343
2013 Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence. Molecular cell 93 23478443
1999 The leukocyte Ig-like receptor (LIR)-1 for the cytomegalovirus UL18 protein displays a broad specificity for different HLA class I alleles: analysis of LIR-1 + NK cell clones. International immunology 93 10050671
2013 Loss of tumor suppressor RPL5/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity. Molecular and cellular biology 83 24061479
2009 Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond-Blackfan anemia. Human mutation 80 19191325
2008 Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor. Proceedings of the National Academy of Sciences of the United States of America 80 18632577
2009 Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. Haematologica 78 19773262
1992 Construction and characterization of a human cytomegalovirus mutant with the UL18 (class I homolog) gene deleted. Journal of virology 64 1328689
2004 Genetic analysis of RpL38 and RpL5, two minute genes located in the centric heterochromatin of chromosome 2 of Drosophila melanogaster. Genetics 56 15520262
2018 SPIN1 promotes tumorigenesis by blocking the uL18 (universal large ribosomal subunit protein 18)-MDM2-p53 pathway in human cancer. eLife 51 29547122
2016 RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response. Leukemia 51 27909306
2002 Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18. BMC structural biology 49 12390682
2004 Specific recognition of the viral protein UL18 by CD85j/LIR-1/ILT2 on CD8+ T cells mediates the non-MHC-restricted lysis of human cytomegalovirus-infected cells. Journal of immunology (Baltimore, Md. : 1950) 45 15100307
1992 The virulence-determining genomic BamHI fragment 4 of pseudorabies virus contains genes corresponding to the UL15 (partial), UL18, UL19, UL20, and UL21 genes of herpes simplex virus and a putative origin of replication. Virology 45 1333128
2020 MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription. Oncogenesis 40 32483207
2014 p53-Independent cell cycle and erythroid differentiation defects in murine embryonic stem cells haploinsufficient for Diamond Blackfan anemia-proteins: RPS19 versus RPL5. PloS one 37 24558476
2007 Human cytomegalovirus-derived protein UL18 alters the phenotype and function of monocyte-derived dendritic cells. Journal of leukocyte biology 36 17898320
2017 Perturbation of RNA Polymerase I transcription machinery by ablation of HEATR1 triggers the RPL5/RPL11-MDM2-p53 ribosome biogenesis stress checkpoint pathway in human cells. Cell cycle (Georgetown, Tex.) 35 29143558
2006 Spontaneous mutations in the human CMV HLA class I homologue UL18 affect its binding to the inhibitory receptor LIR-1/ILT2/CD85j. European journal of immunology 35 16479538
2022 HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia. Blood 33 35213692
2001 Quantity of cytomegalovirus DNA in different leukocyte populations during active infection in vivo and the presence of gB and UL18 transcripts. Journal of medical virology 31 11424116
2016 Transcriptome analysis reveals a ribosome constituents disorder involved in the RPL5 downregulated zebrafish model of Diamond-Blackfan anemia. BMC medical genomics 30 26961822
2004 Transfer of RPS14 and RPL5 from the mitochondrion to the nucleus in grasses. Gene 30 14693379
2007 Increased expression of leukocyte Ig-like receptor-1 and activating role of UL18 in the response to cytomegalovirus infection. Journal of immunology (Baltimore, Md. : 1950) 29 17339449
2020 WDR74 modulates melanoma tumorigenesis and metastasis through the RPL5-MDM2-p53 pathway. Oncogene 27 32005977
2008 Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses. PLoS pathogens 27 18688275
1996 The rpl5-rps14-cob gene arrangement in Solanum tuberosum: rps14 is a transcribed and unedited pseudogene. Plant molecular biology 27 8806426
2017 Mitochondrial Retroprocessing Promoted Functional Transfers of rpl5 to the Nucleus in Grasses. Molecular biology and evolution 26 28541477
2022 Ribosomal protein L5 (RPL5)/ E2F transcription factor 1 (E2F1) signaling suppresses breast cancer progression via regulating endoplasmic reticulum stress and autophagy. Bioengineered 25 35293275
2010 Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis. European journal of human genetics : EJHG 24 20087403
2022 Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway. BMC molecular and cell biology 22 36384455
2016 Leukocyte Immunoglobulin-Like Receptor 1-Expressing Human Natural Killer Cell Subsets Differentially Recognize Isolates of Human Cytomegalovirus through the Viral Major Histocompatibility Complex Class I Homolog UL18. Journal of virology 22 26739048
2007 Variability of UL18, UL40, UL111a and US3 immunomodulatory genes among human cytomegalovirus clinical isolates from renal transplant recipients. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 22 17827058
2002 Human cytomegalovirus (HCMV)-infected endothelial cells and macrophages are less susceptible to natural killer lysis independent of the downregulation of classical HLA class I molecules or expression of the HCMV class I homologue, UL18. Scandinavian journal of immunology 22 11896931
2008 Immune modulation by the human cytomegalovirus-encoded molecule UL18, a mystery yet to be solved. Journal of immunology (Baltimore, Md. : 1950) 21 18096997
2020 Heavy ion radiation-induced DNA damage mediates apoptosis via the Rpl27a-Rpl5-MDM2-p53/E2F1 signaling pathway in mouse spermatogonia. Ecotoxicology and environmental safety 19 32535367
2013 Cis association of leukocyte Ig-like receptor 1 with MHC class I modulates accessibility to antibodies and HCMV UL18. European journal of immunology 19 23348966
1999 Cotranscription of the rpl5-rps14-cob gene cluster in pea mitochondria. Molecular & general genetics : MGG 19 10323235
2004 Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis. Biochemical and biophysical research communications 18 15013438
1993 Ribosomal protein gene rpl5 is cotranscribed with the nad3 gene in Oenothera mitochondria. Molecular & general genetics : MGG 16 8413195
2022 DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer. Cancer medicine 15 35864588
2014 Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia. Pediatric blood & cancer 15 25132370
1998 Transcription of the human cytomegalovirus natural killer decoy gene, UL18, in vitro and in vivo. The Journal of general virology 14 9747719
2004 The rpl5- rps14 mitochondrial region: a hot spot for DNA rearrangements in Solanum spp. somatic hybrids. Current genetics 13 15034752
2022 Olaparib Induces RPL5/RPL11-Dependent p53 Activation via Nucleolar Stress. Frontiers in oncology 12 35719981
2018 Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors. Cancer cell international 12 30479569
2017 Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations. Blood cells, molecules & diseases 12 28376382
2007 Structural elements underlying the high binding affinity of human cytomegalovirus UL18 to leukocyte immunoglobulin-like receptor-1. Journal of molecular biology 12 17869268
2023 RNA-binding motif protein 10 inactivates c-Myc by partnering with ribosomal proteins uL18 and uL5. Proceedings of the National Academy of Sciences of the United States of America 11 38032932
2024 Human cytomegalovirus UL18 prevents priming of MHC-E- and MHC-II-restricted CD8+ T cells. Science immunology 9 39392895
2021 A new murine Rpl5 (uL18) mutation provides a unique model of variably penetrant Diamond-Blackfan anemia. Blood advances 8 34464976
2008 Dissecting the structural determinants of the interaction between the human cytomegalovirus UL18 protein and the CD85j immune receptor. Journal of immunology (Baltimore, Md. : 1950) 8 18178836
2025 hMTR4 promotes p53 protein degradation and tumor growth by accelerating rRNA processing and regulating the RPL5-MDM2 axis. Cell death and differentiation 6 40652043
2024 ZBTB7A interferes with the RPL5-P53 feedback loop and reduces endoplasmic reticulum stress-induced apoptosis of pancreatic cancer cells. Molecular carcinogenesis 6 38896079
2021 Investigation of the molecular causes underlying physical abnormalities in Diamond-Blackfan anemia patients with RPL5 haploinsufficiency. Pathology international 6 34587661
2008 Human cytomegalovirus regulates surface expression of the viral protein UL18 by means of two motifs present in the cytoplasmic tail. Journal of immunology (Baltimore, Md. : 1950) 6 18178837
2021 The Use of B-Cell Polysome Profiling to Validate Novel RPL5 (uL18) and RPL26 (uL24) Variants in Diamond-Blackfan Anemia. Journal of pediatric hematology/oncology 5 33122585
2020 Interaction between the assembly of the ribosomal subunits: Disruption of 40S ribosomal assembly causes accumulation of extra-ribosomal 60S ribosomal protein uL18/L5. PloS one 5 31986150
2019 Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia. Discoveries (Craiova, Romania) 4 32309614
2012 The spectrum of non-classical Diamond-Blackfan anemia: a case of late beginning transfusion dependency associated to a new RPL5 mutation. Pediatric reports 4 22803003
2021 The important role of MDM2, RPL5, and TP53 in mycophenolic acid-induced cleft lip and palate. Medicine 3 34032749
2019 Diamond-Blackfan anemia caused by chromosome 1p22 deletion encompassing RPL5. Human genome variation 3 31645974
2023 A De Novo Frameshift Mutation in RPL5 with Classical Phenotype Abnormalities and Worsening Anemia Diagnosed in a Young Adult-A Case Report and Review of the Literature. Medicina (Kaunas, Lithuania) 2 38004002
2022 Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV. International journal of molecular sciences 2 36361707
2021 Identification of RPL5 gene variants and the risk of hepatic vein thrombosis in Saudi patients. Saudi medical journal 2 34470834
2021 Genetic Variants of RPL5 and RPL9 Genes among Saudi Patients Diagnosed with Thrombosis. Medical archives (Sarajevo, Bosnia and Herzegovina) 2 34483448
2021 The important role of RPS14, RPL5 and MDM2 in TP53-associated ribosome stress in mycophenolic acid-induced microtia. International journal of pediatric otorhinolaryngology 2 34537545
2018 Construction, identification, and immunogenic assessments of an HSV-1 mutant vaccine with a UL18 deletion. Acta virologica 2 29895157
2024 Immune Response Elicited by Recombinant Adenovirus-Delivered Glycoprotein B and Nucleocapsid Protein UL18 and UL25 of HSV-1 in Mice. International journal of molecular sciences 1 39769249
2019 Gene disruption of ribosomal protein L5 (RPL5) decreased the sensitivity of CHO-K1 cells to uncoupler carbonylcyanide-3-chlorophenylhydrazone. Drug discoveries & therapeutics 1 31956228
2017 [The difference expression and diagnostic value of RPL5 in papillary thyroid carcinoma of children and adults]. Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 1 29141292
2026 PRDM16 protects retinal ganglion cells from ischemia-reperfusion Injury by regulating the RPL5/p53 axis. Cellular and molecular life sciences : CMLS 0 41910727
2026 RPS19 and RPL5 haploinsufficient models reveal divergent ribosomal subunit controls of fetal hematopoiesis. Nature communications 0 41951665
2025 Circaea mollis Siebold & Zucc. Induces Apoptosis in Colorectal Cancer Cells by Inhibiting c-Myc Through the Mediation of RPL5. International journal of molecular sciences 0 40429805
2025 RPS19 and RPL5 Haploinsufficient Models Reveal Divergent Ribosomal Subunit Controls of Fetal Hematopoiesis. Research square 0 41041537
2025 Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells. Biochemical pharmacology 0 41177179
2025 RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells. Cell death & disease 0 41413025
2024 RPS19 and RPL5, the most commonly mutated genes in Diamond Blackfan anemia, impact DNA double-strand break repair. bioRxiv : the preprint server for biology 0 39416207
2020 A Novel Deletion in the RPL5 Gene in a Lebanese Child With Diamond Blackfan Anemia Unresponsive to Steroid Treatment. Journal of pediatric hematology/oncology 0 30933022

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