Affinage

RPL11

Large ribosomal subunit protein uL5 · UniProt P62913

Length
178 aa
Mass
20.3 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL11 is a ribosomal protein of the large subunit that functions both as a structural component of the translating ribosome and as a central extraribosomal sensor coupling ribosomal stress to p53 stabilization and c-Myc suppression. Within the ribosome, RPL11's N-terminal domain acts as a conformational switch at the GTPase-associated center, facilitating EF-G-dependent translocation and differentially modulating release factor activities, while its internal P-site loop coordinates tRNA occupancy and translational fidelity (PMID:10338213, PMID:11518530, PMID:6355097, PMID:20705654). Upon nucleolar stress, RPL11 translocates from the nucleolus—where it is normally retained by PICT1, RRS1, and GRWD1—to the nucleoplasm, where it cooperates with RPL5 to bind MDM2 through MDM2's acidic domain and zinc fingers, inhibiting MDM2's E3 ligase activity via a post-ubiquitination mechanism and thereby stabilizing p53; this pathway is regulated by NEDDylation and SUMOylation of RPL11 (PMID:12842086, PMID:15152193, PMID:18560357, PMID:21804542, PMID:26220995, PMID:30024791). RPL11 also directly inhibits c-Myc transcriptional activity by binding Myc Box II and blocking TRRAP recruitment, and independently recruits miRISC (Ago2, miR-24, miR-130a) to c-myc mRNA to promote its degradation, forming a negative feedback loop since RPL11 is itself a c-Myc transcriptional target (PMID:17599065, PMID:21807902, PMID:24141778).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1983 High

    Establishing that L11 is not merely structural but actively modulates translation termination by differentially regulating RF1 and RF2 revealed its first known functional role beyond ribosome assembly.

    Evidence In vitro reconstitution of 50S particles ± L11 with codon-dependent peptidyl-tRNA hydrolysis assays in E. coli

    PMID:6355097

    Open questions at the time
    • Mechanism by which L11 exerts opposite effects on RF1 vs RF2 not resolved
    • No mammalian counterpart demonstrated
  2. 1999 High

    The crystal structure of L11 bound to 23S rRNA revealed that the N-terminal domain functions as a conformational switch at the GTPase-associated center, providing the structural framework for understanding L11's role in factor-dependent translation events and antibiotic resistance.

    Evidence X-ray crystallography of L11–rRNA complex

    PMID:10338213

    Open questions at the time
    • No direct visualization of L11 conformational change during translocation
    • Antibiotic binding site inferred but not directly resolved
  3. 2001 High

    Cryo-EM visualization of EF-G intrusion into the L11 N-terminal domain cleft after GTP hydrolysis established a direct physical link between L11 conformational dynamics and EF-G-dependent translocation.

    Evidence Cryo-EM of wild-type vs L11-minus E. coli ribosomes with EF-G

    PMID:11518530

    Open questions at the time
    • Time-resolved conformational dynamics not captured
    • Functional consequence of disrupting the L11–EF-G arc not tested
  4. 2003 High

    The discovery that RPL11 directly binds MDM2 and inhibits its E3 ligase to stabilize p53 in response to actinomycin D established the first extraribosomal tumor-suppressive function for a ribosomal protein, fundamentally expanding RPL11's role beyond translation.

    Evidence Co-immunoprecipitation and overexpression/knockdown assays in human cells

    PMID:12842086

    Open questions at the time
    • Structural basis of MDM2–RPL11 interaction unknown
    • In vivo relevance not yet demonstrated
  5. 2004 High

    Demonstrating that RPL11 translocates from the nucleolus to the nucleoplasm upon growth inhibition, rather than being transcriptionally or post-translationally regulated, established the nucleolus as a barrier controlling RPL11–MDM2 complex formation.

    Evidence Subcellular fractionation, immunofluorescence, and co-IP in serum-starved cells

    PMID:15152193

    Open questions at the time
    • Signal triggering nucleolar release not identified
    • Mechanism of nucleolar retention unknown
  6. 2006 High

    Revealing that RPL11 inhibits MDM2 through a unique post-ubiquitination mechanism—blocking proteasomal degradation of ubiquitinated MDM2—distinguished its mechanism from other MDM2 regulators including RPL5 and RPL23.

    Evidence In vitro 26S proteasome degradation assay, pulse-chase, and domain-mapping mutagenesis

    PMID:16803902

    Open questions at the time
    • How L11 blocks proteasomal recognition of ubiquitinated MDM2 not resolved
    • Whether this mechanism operates in vivo not confirmed
  7. 2007 High

    Discovery that RPL11 directly binds c-Myc Box II, inhibits TRRAP recruitment and histone acetylation at c-Myc target promoters, and is itself a c-Myc transcriptional target established an extraribosomal negative feedback loop independent of the MDM2–p53 axis.

    Evidence ChIP, co-IP, siRNA knockdown, and overexpression in human cells

    PMID:17599065

    Open questions at the time
    • In vivo significance of the L11–c-Myc feedback loop not tested
    • Structural basis of L11–Myc interaction unknown
  8. 2007 High

    The crystal structure of PrmA methyltransferase complexed with L11 revealed how L11 is trimethylated at its N-terminus and two lysines prior to ribosome assembly, establishing the first structurally characterized post-translational modification of L11.

    Evidence X-ray crystallography at 2.4 Å of PrmA–L11 complex in multiple orientations

    PMID:17215866

    Open questions at the time
    • Functional consequence of L11 methylation on translation or extraribosomal functions not determined
  9. 2008 High

    Demonstrating that RPL5 and RPL11 cooperate to inhibit MDM2, and that L11's 5S rRNA-binding ability is required for this cooperation, established the 5S RNP as the functional unit of ribosomal stress surveillance.

    Evidence In vitro ubiquitination assay, co-IP, and L11 5S rRNA-binding mutant analysis

    PMID:18305114 PMID:18560357

    Open questions at the time
    • Stoichiometry of the L5–L11–5S rRNA–MDM2 complex not determined
    • Whether 5S rRNA plays a direct role in MDM2 binding unknown
  10. 2009 High

    Zebrafish rpl11 loss activated p53-dependent apoptosis in the brain, rescued by p53 knockdown, providing the first in vivo vertebrate genetic evidence that RPL11 deficiency activates p53 and causes developmental defects reminiscent of ribosomopathies.

    Evidence Morpholino knockdown in zebrafish with double-knockdown epistasis and TUNEL assay

    PMID:19129914

    Open questions at the time
    • Whether the phenotype reflects extraribosomal RPL11 function vs translational insufficiency not resolved
  11. 2009 High

    Showing that 40S biogenesis defects increase RPL11 translation via 5'-TOP mRNA upregulation, activating p53 without nucleolar disruption, demonstrated a nucleolus-independent arm of the RPL11–MDM2–p53 pathway.

    Evidence Polysome profiling, siRNA knockdown of rpS6, immunofluorescence for nucleolar integrity, double-KD rescue

    PMID:19287375

    Open questions at the time
    • Translational regulation mechanism of RPL11 5'-TOP mRNA not fully elucidated
  12. 2010 High

    Identification of NEDDylation as essential for RPL11 nuclear retention and p53 activation, and the finding that L11's conserved P-site loop regulates tRNA occupancy and translational fidelity, expanded understanding of L11 regulation in both extraribosomal and ribosomal contexts.

    Evidence siRNA epistasis with NEDD8 knockdown and ubiquitination assays (NEDDylation); chemical probing and site-directed mutagenesis of yeast L11 P-site loop (translation)

    PMID:20554519 PMID:20705654

    Open questions at the time
    • NEDDylation sites on RPL11 not mapped
    • Interplay between P-site loop conformation and extraribosomal functions unexplored
  13. 2011 High

    Three parallel advances established that PICT1 retains RPL11 in the nucleolus (loss of PICT1 activates p53), that RPL11 recruits miRISC to c-myc mRNA for degradation, and that RPL11 is recruited to p53 target gene promoters where it promotes p300/CBP recruitment and p53 acetylation, collectively defining both the upstream gate and downstream effector mechanisms of extraribosomal RPL11.

    Evidence PICT1-KO mouse/ES cells with IP and ubiquitination assays; RNA-IP and Ago2 co-IP with KD epistasis; ChIP at p53 target promoters with NEDDylation requirement

    PMID:21804542 PMID:21807902 PMID:22081073

    Open questions at the time
    • How PICT1 physically sequesters RPL11 in the nucleolus not structurally resolved
    • Whether RPL11 promoter recruitment is direct or MDM2-dependent unclear
  14. 2012 High

    Demonstration that RPL5 and RPL11 mutually protect each other from proteasomal degradation upon Pol I inhibition, selectively accumulating in the ribosome-free fraction, explained how only these two ribosomal proteins persist as free MDM2 inhibitors during nucleolar stress.

    Evidence Pulse-chase, proteasome inhibitor treatment, co-IP, and immunofluorescence in human cells

    PMID:23169665

    Open questions at the time
    • Mechanism of mutual protection (direct shielding vs chaperone-mediated) not determined
  15. 2013 High

    RPL5 and RPL11 were shown to co-operatively guide RISC (via TRBP and Ago2) to c-myc mRNA 3'-UTR, and separately, loss of RPL5/RPL11 was found to impede cell cycle progression through reduced translational capacity rather than inducing arrest, refining understanding of their dual tumor-suppressive mechanisms.

    Evidence RNA-IP and protein IP for RPL5–Ago2–TRBP–c-myc mRNA; ribosome profiling and cell cycle analysis in primary fibroblasts

    PMID:24061479 PMID:24141778

    Open questions at the time
    • Whether miRISC guidance requires the 5S RNP or free RPL5/RPL11 not determined
  16. 2014 High

    RPL11 was found to activate TAp73 independently of MDM2, displacing MDM2 from TAp73 target promoters, revealing an extraribosomal surveillance mechanism that extends beyond p53 to other p53 family members.

    Evidence Co-IP of L11–TAp73, ChIP showing MDM2 displacement, siRNA KD with apoptosis assays

    PMID:25301064

    Open questions at the time
    • Structural basis of L11–TAp73 interaction unknown
    • Physiological contexts where TAp73 axis predominates over p53 axis not defined
  17. 2015 High

    The 2.4 Å crystal structure of MDM2–RPL11 revealed that MDM2 mimics 28S rRNA to bind RPL11 through its acidic domain and zinc fingers, with the C4 zinc finger specifically determining RPL11 selectivity, providing the atomic-level explanation for how ribosomal stress is transduced to p53 stabilization.

    Evidence X-ray crystallography, MDM2 mutagenesis, cellular p53 activation assays

    PMID:26220995

    Open questions at the time
    • Structure of the full 5S RNP–MDM2 complex not available
    • Conformational dynamics of the interaction in solution not captured
  18. 2015 High

    Rpl11 haploinsufficiency in mice caused anemia, defective erythroid maturation, elevated c-Myc levels, and lymphoma susceptibility with impaired p53 activation, providing definitive mammalian genetic evidence linking RPL11 dosage to both ribosomopathy-like phenotypes and tumor suppression.

    Evidence Conditional Rpl11 heterozygous mouse, bone marrow transplantation, irradiation-induced lymphomagenesis

    PMID:26489471

    Open questions at the time
    • Whether anemia is p53-dependent or translation-dependent not fully dissected
    • Human RPL11 mutations in Diamond-Blackfan anemia not directly studied here
  19. 2016 High

    GRWD1 was identified as a nucleolar protein that physically interacts with RPL11 and competitively inhibits RPL11–MDM2 binding, establishing a second nucleolar retention factor (alongside PICT1) that gates the ribosomal stress response.

    Evidence Competitive co-IP, in vitro ubiquitination assay, domain mapping, immunofluorescence

    PMID:27856536

    Open questions at the time
    • Relative contributions of PICT1, GRWD1, and RRS1 to RPL11 retention not compared quantitatively
  20. 2018 Medium

    Discovery that SUMOylation of RPL11 promotes its nucleolar exit while antagonizing NEDDylation added a layer of PTM crosstalk governing RPL11 localization and p53 activation.

    Evidence In vivo SUMOylation/NEDDylation assays, Ubc9 knockdown, immunofluorescence

    PMID:30024791

    Open questions at the time
    • SUMOylation sites on RPL11 not mapped
    • How SUMO and NEDD8 modifications are temporally coordinated not resolved
    • Independent replication needed
  21. 2021 Medium

    RRS1 was identified as a third nucleolar retention factor for RPL11, and the lncRNA PiHL was found to sequester RPL11 by enhancing the GRWD1–RPL11 interaction, revealing RNA-mediated regulation of the RPL11–MDM2–p53 axis.

    Evidence Co-IP, RNA pulldown/RIP, in vivo ubiquitination assays for RRS1 and PiHL studies

    PMID:31903119 PMID:34433556

    Open questions at the time
    • Whether RRS1 and GRWD1 act in the same or parallel retention pathways not determined
    • PiHL mechanism characterized in cancer cell lines only
  22. 2022 Medium

    RPS27a was shown to directly bind RPL11, and its depletion enhanced RPL11–MDM2 binding to activate p53, revealing a cross-subunit ribosomal protein interaction that modulates the nucleolar stress response.

    Evidence GST pulldown, co-IP, in vitro ubiquitination, siRNA epistasis

    PMID:35073964

    Open questions at the time
    • Whether the RPS27a–RPL11 interaction occurs on or off the ribosome not determined
    • Single lab observation awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structure of the complete 5S RNP–MDM2 signaling complex, how multiple nucleolar retention factors (PICT1, GRWD1, RRS1) are coordinately regulated, the full spectrum of RPL11 PTM crosstalk (SUMO/NEDD8/methylation) and its functional hierarchy, and whether RPL11's ribosomal and extraribosomal functions are mechanistically linked through shared conformational states.
  • No structure of the complete 5S RNP–MDM2 complex
  • Quantitative model of PICT1/GRWD1/RRS1 gate lacking
  • RPL11 PTM crosstalk hierarchy unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2
Localization
GO:0005730 nucleolus 3 GO:0005840 ribosome 3 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
AGO2GRWD1MDM2MYCPICT1RPL5RRS1TP73
Complex memberships
5S RNP (RPL5-RPL11-5S rRNA)60S ribosomal subunit

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 RPL11 (L11) directly interacts with HDM2 (MDM2) and inhibits its E3 ubiquitin ligase function, leading to stabilization and activation of p53. Enhancement of endogenous L11–HDM2 interaction occurs after treatment with low-dose actinomycin D, revealing a novel pathway for p53 stabilization in response to perturbations in ribosome biogenesis. Co-immunoprecipitation, overexpression/knockdown functional assays, actinomycin D treatment Cancer Cell High 12842086
2004 RPL11 is not regulated transcriptionally or by protein stability under serum starvation; instead, growth inhibition triggers translocation of L11 from the nucleolus to the nucleoplasm, where it forms a complex with HDM2 to activate p53. The nucleolus acts as a barrier preventing L11–HDM2 interaction during normal growth. Subcellular fractionation, siRNA knockdown, co-immunoprecipitation, immunofluorescence The EMBO Journal High 15152193
2006 RPL11 uniquely inhibits MDM2 turnover through a post-ubiquitination mechanism: L11 leads to accumulation of ubiquitinated MDM2 and inhibits 26S proteasome-mediated degradation of ubiquitinated MDM2, prolonging MDM2 half-life. This requires the central MDM2-binding domain (residues 51–108) of L11 and MDM2's ubiquitin ligase activity, distinguishing L11's mechanism from that of L5 and L23. In vitro 26S proteasome degradation assay, pulse-chase half-life measurements, domain-mapping with deletion mutants, co-immunoprecipitation The Journal of Biological Chemistry High 16803902
2007 RPL11 binds to the Myc Box II (MB II) domain of c-Myc, inhibits recruitment of the coactivator TRRAP, and reduces histone H4 acetylation at c-Myc target gene promoters, thereby inhibiting c-Myc transcriptional activity and cell proliferation. L11 is itself a transcriptional target of c-Myc, forming a negative feedback loop. L11 also regulates c-Myc protein and mRNA levels. Co-immunoprecipitation, ChIP assay, siRNA knockdown, overexpression, proliferation assays The EMBO Journal High 17599065
2008 L11 cooperates with ribosomal protein L5 to robustly inhibit MDM2 E3 ligase activity and stabilize p53. L11 alone is less potent than p14ARF, but cooperation with L5 approaches p14ARF-level p53 activation. The ability of L11 to bind 5S rRNA is required for this cooperation with L5. Co-immunoprecipitation, in vitro ubiquitination assay, L11 mutant (unable to bind 5S rRNA) analysis Oncogene High 18560357
2008 MPA (mycophenolic acid) treatment inhibits pre-rRNA synthesis and disrupts the nucleolus, enhancing MDM2 interaction with L5 and L11. Knockdown of L5 or L11 markedly impairs MPA-induced p53 induction and G1 cell cycle arrest, demonstrating that L5 and L11 mediate p53 activation downstream of nucleolar stress caused by guanine nucleotide depletion. siRNA knockdown, co-immunoprecipitation, cell cycle analysis, pre-rRNA synthesis measurement The Journal of Biological Chemistry High 18305114
2009 Impairment of 40S ribosome biogenesis (via rpS6 depletion) does not disrupt nucleolar integrity but selectively upregulates translation of 5'-TOP mRNAs including rpL11 mRNA, increasing free rpL11 protein which then inhibits MDM2 to activate p53. This pathway operates without nucleolar disruption. siRNA knockdown, polysome profiling, immunofluorescence (nucleolar integrity), p53 rescue by double KD Nature Cell Biology High 19287375
2009 Loss of rpl11 in zebrafish activates the p53 pathway and causes p53-dependent apoptosis predominantly in the brain, leading to embryonic developmental defects. Simultaneous knockdown of p53 rescues the developmental phenotype, placing rpl11 upstream of p53 in a checkpoint response to ribosomal dysfunction in vivo. Morpholino knockdown in zebrafish, TUNEL apoptosis assay, double knockdown (rpl11 + p53) epistasis, gene expression analysis PLoS ONE High 19129914
2011 PICT1 (GLTSCR2) is a nucleolar protein that retains RPL11 in the nucleolus. Loss of PICT1 releases RPL11 from nucleoli, enabling increased RPL11–MDM2 binding, which blocks MDM2-mediated p53 ubiquitination, leading to p53 accumulation and p53-dependent G1 arrest and apoptosis even without DNA damage. Pict1-knockout mouse/ES cells, co-immunoprecipitation (Pict1–Rpl11, Rpl11–Mdm2), immunofluorescence localization, in vitro ubiquitination assay Nature Medicine High 21804542
2011 RPL11 recruits miR-24 and the RISC component Ago2 to the 3'-UTR of c-myc mRNA, promoting c-myc mRNA degradation. Ribosome-free L11 re-localizes from the nucleolus to the cytoplasm in response to ribosomal stress (actinomycin D or 5-fluorouracil), enhancing its association with Ago2, miR-24, and c-myc mRNA. Ablation of Ago2 abrogates L11-mediated c-myc mRNA reduction. RNA immunoprecipitation, co-immunoprecipitation (L11-Ago2), mRNA stability assay, siRNA knockdown of L11/Ago2, qRT-PCR, subcellular fractionation Molecular and Cellular Biology High 21807902
2011 RPL11 is rapidly recruited to promoters of p53-regulated genes upon nucleolar stress, where it is required for recruitment of co-activators p300/CBP and p53 K382 acetylation. Direct binding of L11 to MDM2 and NEDDylation of L11 are both required for L11 promoter recruitment. L11 at promoters relieves MDM2-mediated transcriptional repression of p53. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, knockdown experiments, NEDD8 analysis Oncogene High 22081073
2012 Among newly synthesized ribosomal proteins, L5 and L11 are selectively protected from proteasomal degradation upon inhibition of Pol I activity. Free L5 and L11 mutually protect each other from proteasomal degradation, accumulate in the ribosome-free fraction, and bind MDM2. Disrupted nucleoli provide a platform for L5- and L11-dependent p53 activation. Pulse-chase protein synthesis, proteasome inhibitor treatment, co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown PNAS High 23169665
2010 Knockdown of 60S ribosomal proteins L29 or L30 activates p53 in an L11- and L5-dependent manner (epistasis). This is accompanied by enhanced MDM2 interaction with L11 and L5, inhibited MDM2-mediated p53 ubiquitination, and increased NEDDylation and nuclear retention of L11. NEDD8 knockdown suppresses p53 activation, revealing NEDDylation of L11 as a critical step in the ribosomal stress–p53 pathway. siRNA knockdown epistasis, co-immunoprecipitation, in vitro ubiquitination assay, NEDDylation analysis The Journal of Biological Chemistry High 20554519
2013 RPL5 cooperates with RPL11 to guide RISC (via TRBP and Ago2) to c-Myc mRNA 3'-UTR, mediating c-myc mRNA degradation. RPL5 binds the 3'-UTR of c-myc mRNA and two RISC subunits. RPL5 and RPL11 co-reside on c-myc mRNA and co-operatively suppress c-Myc expression. Co-immunoprecipitation (RPL5–Ago2, RPL5–TRBP), RNA immunoprecipitation (RPL5–c-myc mRNA), siRNA knockdown, overexpression Oncogene High 24141778
2013 Loss of RPL5/RPL11 in primary human lung fibroblasts does not induce cell cycle arrest (unlike other tumor suppressors) but impedes cell cycle progression by reducing ribosome content and translational capacity, which suppresses cyclin accumulation at the translational level. siRNA knockdown in primary fibroblasts, ribosome profiling, flow cytometry cell cycle analysis, polysome analysis Molecular and Cellular Biology High 24061479
2014 RPL11 and L5 activate TAp73 transcriptional activity by directly associating with the transactivation domain of TAp73 (independently of MDM2), displacing MDM2 from TAp73 target gene promoters and inducing TAp73-mediated apoptosis. This reveals a distinct mechanism from the L11–MDM2–p53 axis. Co-immunoprecipitation (L11–TAp73, L5–TAp73), ChIP of MDM2 at TAp73 target promoters, siRNA knockdown, apoptosis assays Cell Death and Differentiation High 25301064
2014 Nuclear PRAS40 (phosphorylated by Akt at T246 and mTORC1 at S221) physically associates with RPL11, negatively regulating the RPL11–HDM2–p53 nucleolar stress response pathway and suppressing p53-mediated cellular senescence. A PRAS40 mutant (T246A) unable to bind RPL11 cannot rescue p53 upregulation upon PRAS40 silencing. Co-immunoprecipitation (PRAS40–RPL11), siRNA knockdown, mutagenesis (PRAS40 T246A), senescence assays Oncogene Medium 24704832
2015 Crystal structure of human MDM2 complexed with RPL11 at 2.4 Å reveals that MDM2 interacts with RPL11 through its acidic domain and two zinc fingers, inducing conformational changes in both proteins. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc finger of MDM2 specifically determines RPL11 binding but not MDMX binding. MDM2 mutants unable to bind RPL11 fail to be inhibited by RPL11 and cannot activate p53 in cells. X-ray crystallography (2.4 Å), MDM2 mutagenesis, cellular p53 activation assays Genes & Development High 26220995
2015 Partial loss of Rpl11 (heterozygous deletion) in adult mice causes anemia with decreased erythroid progenitors and defective erythroid maturation, increased susceptibility to lymphomagenesis, and compromised p53 activation upon ribosomal stress or DNA damage. Fibroblasts and hematopoietic tissues from Rpl11 heterozygous mice show higher basal cMYC levels. Conditional Rpl11 heterozygous mouse model, bone marrow transplantation, irradiation-induced lymphomagenesis, p53 activation assays, flow cytometry Cell Reports High 26489471
2015 RPL11 promotes miR-130a-loaded miRISC to target and degrade c-myc mRNA in response to UV-induced DNA damage. UV treatment promotes binding of L11 to miR-130a, Ago2, and c-myc mRNA, and re-localizes L11 from the nucleolus to the cytoplasm where it associates with c-myc mRNA. RNA immunoprecipitation, co-immunoprecipitation (L11–Ago2), mRNA stability assay, miRNA inhibitor, immunofluorescence localization Oncotarget Medium 25544755
2016 GRWD1 physically interacts with RPL11, localizes to nucleoli and is released upon nucleolar stress. GRWD1 overexpression competitively inhibits the RPL11–MDM2 interaction and alleviates RPL11-mediated suppression of MDM2 ubiquitin ligase activity toward p53. The N-terminal acidic domain of GRWD1 mediates this competitive inhibition. Co-immunoprecipitation (GRWD1–RPL11, RPL11–MDM2 competition), in vitro ubiquitination assay, siRNA/overexpression, immunofluorescence EMBO Reports High 27856536
2018 RPL11 is covalently modified by SUMO1 and SUMO2. SUMOylation negatively modulates NEDD8 conjugation to RPL11 and promotes RPL11 translocation outside of nucleoli. The SUMO-conjugating enzyme Ubc9 is required for RPL11-mediated p53 activation. SUMOylation of RPL11 is triggered by ribosomal stress and ARF upregulation. In vivo SUMOylation assay, NEDDylation assay, Ubc9 knockdown, immunofluorescence localization, p53 activation assays FASEB Journal Medium 30024791
2020 Long noncoding RNA PiHL sequesters RPL11 from MDM2 by enhancing GRWD1–RPL11 complex formation, thereby promoting MDM2-mediated p53 ubiquitination and degradation. p53 can directly bind the PiHL promoter, forming a regulatory feedback loop. Co-immunoprecipitation (GRWD1–RPL11, RPL11–MDM2), in vitro ubiquitination assay, RNA pulldown/RIP, luciferase reporter for p53-PiHL promoter Theranostics Medium 31903119
2021 RRS1 promotes retention of RPL11 in the nucleolus, attenuating ribosomal stress signaling and potentiating MDM2-mediated ubiquitination and degradation of p53. RRS1 knockdown releases RPL11 from nucleoli, increasing RPL11–MDM2 binding and p53 levels. RRS1 overexpression/knockdown, co-immunoprecipitation (RRS1–RPL11, RPL11–MDM2), in vivo ubiquitination assay, immunofluorescence Science Advances Medium 34433556
2022 RPS27a directly binds RPL11 (demonstrated by GST pulldown and co-IP). RPS27a knockdown weakens the RPS27a–RPL11 interaction but enhances RPL11–MDM2 binding, thereby inhibiting MDM2-mediated p53 ubiquitination and degradation in an RPL11-dependent manner. GST pulldown, co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown epistasis Journal of Experimental & Clinical Cancer Research Medium 35073964
2007 Crystal structure of the PrmA methyltransferase–L11 complex (at 2.4 Å) shows that PrmA post-translationally trimethylates the N-terminal alpha-amino group and epsilon-amino groups of Lys3 and Lys39 of L11. PrmA positions L11 in multiple orientations for consecutive methylation reactions, targeting L11 preferentially before its assembly into the 50S subunit. X-ray crystallography, enzyme-substrate complex structures in multiple orientations The EMBO Journal High 17215866
1999 Crystal structure of the 58-nucleotide 23S rRNA fragment bound to ribosomal protein L11 reveals that the C-terminal domain of L11 binds RNA tightly while the N-terminal domain makes limited RNA contacts and is proposed to function as a conformational switch. Thiostrepton/micrococcin resistance mutations line a cleft between RNA and the N-terminal domain, suggesting the antibiotics bind in this cleft to lock the switch. X-ray crystallography of L11–rRNA complex Cell High 10338213
2001 By comparing cryo-EM reconstructions of wild-type and L11-minus E. coli ribosomes, L11 was localized at the base of the L7/L12 stalk. After EF-G-dependent GTP hydrolysis, domain V of EF-G intrudes into the cleft between 23S rRNA and the N-terminal domain of L11, causing the L11 N-terminal domain to move and form an arc-like connection with the G' domain of EF-G, thus mechanistically linking L11 to EF-G-dependent translocation. Cryo-electron microscopy reconstruction, difference mapping with L11-minus mutant ribosomes, molecular modeling Journal of Molecular Biology High 11518530
2010 Yeast ribosomal protein L11 contains a conserved, positively charged internal P-site loop that interacts with the tRNA T-loop. The loop is inherently flexible: it extends into the ribosomal P-site when unoccupied by tRNA and retracts when tRNA is bound. Mutations in this loop alter P-site tRNA affinity, A-site tRNA binding, translational fidelity, and virus maintenance. Chemical protection assays, site-directed mutagenesis of P-site loop, functional assays for translational fidelity/drug sensitivity Nucleic Acids Research High 20705654
2012 Ribosomal stress (actinomycin D or L37 depletion) activates p53 in an L11-dependent manner in mouse embryonic stem cells and induced pluripotent stem cells, resulting in transcriptional induction of p53 targets and L11- and p53-dependent apoptosis. siRNA knockdown (L11 and L37), actinomycin D treatment, p53 activation assays, apoptosis assays in ESC/iPSC Cell Cycle Medium 22262176
1983 Ribosomal protein L11 of E. coli (an ortholog of mammalian RPL11) differentially regulates the two peptide chain release factors: L11 is required for efficient RF1-dependent peptide release at UAG codons, while its presence suppresses RF2-dependent release at UGA codons (RF2 has lower apparent Km for termination codon in L11-minus ribosomes). This is the first demonstration of opposite effects of a ribosomal protein on the two release factors. Reconstitution of 50S particles with and without L11, codon-dependent peptidyl-tRNA hydrolysis assay, kinetic analysis The Journal of Biological Chemistry High 6355097

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Regulation of HDM2 activity by the ribosomal protein L11. Cancer cell 550 12842086
1999 A detailed view of a ribosomal active site: the structure of the L11-RNA complex. Cell 286 10338213
2009 Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction. Nature cell biology 261 19287375
2008 Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Molecular cell 235 18406324
2004 Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation. The EMBO journal 217 15152193
2012 Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress. Proceedings of the National Academy of Sciences of the United States of America 184 23169665
2007 Inhibition of c-Myc activity by ribosomal protein L11. The EMBO journal 162 17599065
2011 Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nature medicine 153 21804542
1983 Localization of the target site for translational regulation of the L11 operon and direct evidence for translational coupling in Escherichia coli. Cell 125 6354472
2009 Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response. PloS one 122 19129914
2008 Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway. Oncogene 112 18560357
2006 Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism. The Journal of biological chemistry 103 16803902
1991 Association of DNA helicase and primase activities with a subassembly of the herpes simplex virus 1 helicase-primase composed of the UL5 and UL52 gene products. Proceedings of the National Academy of Sciences of the United States of America 102 1847509
1992 The six conserved helicase motifs of the UL5 gene product, a component of the herpes simplex virus type 1 helicase-primase, are essential for its function. Journal of virology 100 1309257
2000 Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2. Journal of virology 96 10933704
1998 The antibiotic thiostrepton inhibits a functional transition within protein L11 at the ribosomal GTPase centre. Journal of molecular biology 95 9512711
2011 Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress. Molecular and cellular biology 94 21807902
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