Affinage

RPL34

Large ribosomal subunit protein eL34 · UniProt P49207

Round 2 corrected
Length
117 aa
Mass
13.3 kDa
Annotated
2026-04-28
68 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL34 (eL34) is a core structural component of the 60S large ribosomal subunit that facilitates ribosome assembly and possesses extra-ribosomal regulatory activities. Cryo-EM structures of the human 80S ribosome place RPL34 within the large subunit core (PMID:23636399, PMID:25901680), and genetic and biochemical studies in Bacillus subtilis demonstrate that L34 promotes 70S ribosome formation by functionally substituting for Mg²⁺ during subunit joining (PMID:25182490). Outside the ribosome, RPL34 selectively inhibits p35-activated Cdk5 and Cdk4/cyclin D1 kinase activities (PMID:10049762), and its protein stability is regulated by CAND1-mediated reduction of ubiquitination (PMID:37427415). Bacterial L34 physically interacts with ornithine decarboxylase and arginine decarboxylase to suppress polyamine biosynthesis, indicating a conserved capacity for extra-ribosomal enzyme regulation (PMID:7539334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1989 Medium

    Determination of the primary structure of rat RPL34 (117 residues, Mr 13,498) established the molecular identity of this ribosomal protein and revealed it is encoded by a multicopy gene family.

    Evidence cDNA sequencing, NH2-terminal protein sequencing, and Southern hybridization in rat

    PMID:2721685

    Open questions at the time
    • No functional data; structural role within the ribosome unknown at this stage
  2. 1995 Medium

    Discovery that E. coli L34 physically interacts with ornithine and arginine decarboxylases and specifically inhibits their activities established the first extra-ribosomal function for L34, linking it to polyamine metabolism.

    Evidence Immunoprecipitation, in vivo overexpression of L34 and enzyme activity assays with specificity controls in E. coli

    PMID:7539334

    Open questions at the time
    • Demonstrated in bacteria; relevance to eukaryotic RPL34 not tested
    • Mechanism of inhibition (competitive, allosteric) not defined
    • No structural data on the L34–decarboxylase interaction
  3. 1999 Medium

    Identification of RPL34 as a selective inhibitor of Cdk5 (p35-activated) and Cdk4/cyclin D1 — but not Cdk2/cyclin A — revealed a mammalian extra-ribosomal function connecting RPL34 to cell-cycle kinase regulation.

    Evidence Yeast two-hybrid screen from HeLa cDNA library, in vitro kinase inhibition assays

    PMID:10049762

    Open questions at the time
    • No in vivo validation of Cdk5/Cdk4 inhibition by endogenous RPL34
    • Binding interface not mapped; no mutagenesis or structural data
    • Unclear whether ribosome-free RPL34 pool is sufficient for kinase regulation in cells
  4. 2013 High

    Cryo-EM resolution of the human 80S ribosome confirmed RPL34 as a bona fide structural component of the 60S subunit, grounding all prior sequence-level assignments in a physical structure.

    Evidence High-resolution cryo-EM of the human 80S ribosome with atomic model building

    PMID:23636399

    Open questions at the time
    • Position resolved but specific contacts and functional contribution within the subunit not dissected
  5. 2014 High

    Genetic deletion and suppressor analysis in B. subtilis showed that L34 is required for efficient 70S ribosome formation and that its function can be bypassed by elevated Mg²⁺, establishing L34 as a facilitator of subunit joining that functionally substitutes for divalent cations.

    Evidence Bacterial genetics (rpmH deletion, suppressor mutations in yhdP/mgtE), sucrose gradient sedimentation, in vitro subunit association assay with varying Mg²⁺

    PMID:25182490

    Open questions at the time
    • Demonstrated in bacteria; whether eukaryotic RPL34 plays an analogous role in 80S assembly not tested
    • Structural basis for Mg²⁺ mimicry not determined
  6. 2015 High

    A near-atomic (2.9 Å core) cryo-EM structure of the human 80S ribosome independently replicated RPL34's positioning within the 60S subunit at higher resolution.

    Evidence Single-particle cryo-EM at 3.6 Å average resolution

    PMID:25901680

    Open questions at the time
    • Functional contribution of RPL34 to human translation still inferred from lower organisms
  7. 2016 Low

    RPL34 knockdown in pancreatic cancer cells produced cell-cycle arrest, apoptosis, and altered MAPK/p53 pathway gene expression, suggesting RPL34 expression level influences growth-regulatory signaling in cancer cells.

    Evidence shRNA knockdown, flow cytometry, gene expression profiling, xenograft assay in pancreatic cancer cells

    PMID:27845896

    Open questions at the time
    • Pathway changes inferred from expression profiling, not direct mechanistic interaction
    • Knockdown of an essential ribosomal protein may cause global translational effects that confound pathway-specific claims
    • Single cancer type, no rescue experiments
  8. 2017 Low

    RPL34 silencing reduced phospho-PI3K and phospho-Akt levels in esophageal cancer cells, extending the oncogenic signaling associations of RPL34 to the PI3K/Akt axis.

    Evidence shRNA knockdown, western blot for p-PI3K/p-Akt, xenograft assay

    PMID:28109079

    Open questions at the time
    • No direct binding or mechanistic link between RPL34 and PI3K pathway components
    • Global translational defects from ribosomal protein depletion not controlled for
  9. 2023 Medium

    Identification of CAND1 as a physical interactor that stabilizes RPL34 by reducing its ubiquitination provided the first mechanism governing RPL34 protein turnover, and epistasis experiments linked RPL34 to JAK2/STAT3 activation and EMT in colorectal cancer.

    Evidence Immunoprecipitation, ubiquitination assays, overexpression/knockdown epistasis, in vitro and in vivo CRC models

    PMID:37427415

    Open questions at the time
    • The E3 ligase responsible for RPL34 ubiquitination not identified
    • Whether CAND1 stabilization of RPL34 affects ribosome biogenesis versus extra-ribosomal pools not distinguished
    • Single study; independent replication needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether the extra-ribosomal functions of human RPL34 — Cdk5/Cdk4 inhibition, potential polyamine regulation, and signaling pathway modulation — operate via a free cytosolic pool or require release from ribosomes, and no structural basis for any of these moonlighting interactions has been determined.
  • No quantification of ribosome-free RPL34 in human cells
  • No structural or mutagenesis data for any extra-ribosomal interaction
  • Role of RPL34 in human 80S subunit joining not directly tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 3
Partners
CAND1CDK4CDK5
Complex memberships
60S large ribosomal subunit80S ribosome

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human 60S ribosomal protein L34 was identified as a Cdk5-interacting protein via yeast two-hybrid screen of a HeLa cDNA library. Biochemical analyses demonstrated that L34 cannot activate Cdk5 but potently inhibits p35-activated Cdk5 kinase activity. L34 also interacts with Cdk4 and inhibits Cdk4/cyclin D1 activity, but does not interact with Cdk2 or inhibit Cdk2/cyclin A, indicating selectivity. Yeast two-hybrid screen, in vitro kinase inhibition assay Biochemical and biophysical research communications Medium 10049762
2016 Knockdown of RPL34 in pancreatic cancer cells caused cell cycle arrest at G2 phase, apoptosis, suppression of proliferation, colony formation, migration, and drug resistance. Gene expression profiling after RPL34 silencing revealed alteration of MAPK and p53 signaling pathways, placing RPL34 upstream of these pathways in pancreatic cancer cells. shRNA knockdown, flow cytometry, gene expression profiling, in vivo xenograft assay Oncotarget Low 27845896
2017 Knockdown of RPL34 in esophageal cancer cells significantly downregulated phospho-PI3K and phospho-Akt protein levels, indicating that RPL34 modulates esophageal cancer cell proliferation and invasion in part through the PI3K/Akt signaling pathway. lentivirus-mediated shRNA knockdown, western blot for p-PI3K and p-Akt, in vitro proliferation/invasion assays, nude mouse xenograft Oncology research Low 28109079
2018 Knockdown of RPL34 in glioma cells significantly downregulated phospho-JAK and phospho-STAT3 levels, inhibited proliferation, migration, invasion, and prevented epithelial-mesenchymal transition, indicating RPL34 promotes glioma progression through the JAK/STAT3 signaling pathway. shRNA knockdown, western blot for p-JAK and p-STAT3, proliferation/invasion/migration assays Journal of cellular biochemistry Low 30216512
2021 RPL34 was found to act as a tumor suppressor in cervical cancer and regulate cell proliferation through the MDM2-P53 pathway. Experiments using Actinomycin D, MDM2 inhibitor, and western blotting demonstrated that RPL34 modulates MDM2-P53 signaling. Additionally, RNA-binding protein immunoprecipitation (RIP) assay identified that EIF4A3 binds to and regulates RPL34-AS1, which in turn regulates RPL34 expression. Quantitative proteomics, western blotting with MDM2 inhibitor and Actinomycin D treatment, RIP assay Cancer science Low 33675124
2022 RPL34 suppression in glioblastoma cells induced apoptosis through activation of the Bad/Caspase-7/PARP signaling pathway, as demonstrated by loss-of-function experiments with defined apoptotic readouts. shRNA knockdown, western blot for Bad, Caspase-7, and PARP activation, cell proliferation assay Applied biochemistry and biotechnology Low 35377127
2023 Immunoprecipitation identified CAND1 (cullin-associated NEDD8-dissociated protein 1) as an RPL34-interacting protein in colorectal cancer cells. CAND1 overexpression reduced RPL34 ubiquitination and stabilized RPL34 protein, while CAND1 silencing reduced proliferation and invasion. RPL34 overexpression activated the JAK2/STAT3 pathway and induced EMT; RPL34 knockdown rescued CAND1-induced CRC progression. Immunoprecipitation, ubiquitination assay, western blot, overexpression and knockdown experiments, in vitro and in vivo assays Human gene therapy Medium 37427415
2013 RPL34 (eL34) was resolved as a component of the 60S large ribosomal subunit in the cryo-EM structure of the human 80S ribosome, confirming its structural incorporation into the mature human ribosome. High-resolution cryo-electron microscopy, atomic model building Nature High 23636399
2015 RPL34 was confirmed as a structural component of the human 60S ribosomal subunit in the near-atomic (3.6 Å average, 2.9 Å in core) cryo-EM structure of the human 80S ribosome, providing atomic-level detail of its positioning within the large subunit. Single-particle cryo-electron microscopy, atomic model building Nature High 25901680
1995 E. coli ribosomal protein L34 (and S20) were shown to physically interact with ornithine decarboxylase and arginine decarboxylase by immunoprecipitation, and in vivo overexpression of L34 (but not eight other ribosomal proteins) specifically lowered the activities of these enzymes and decreased total polyamine production through reversible post-translational inhibition. Overexpression of ornithine decarboxylase reciprocally elevated S20 and L34 levels specifically. In vivo overexpression, enzyme activity assays, immunoprecipitation with immunoblot The international journal of biochemistry & cell biology Medium 7539334
2014 In Bacillus subtilis, deletion of rpmH (encoding ribosomal protein L34) caused severe slow growth and a defect in 70S ribosome formation. Suppressor mutations increasing intracellular Mg2+ (via yhdP disruption or mgtE overexpression) restored both 70S formation and growth. In vitro subunit association experiments showed that 50S subunits lacking L34 could only form 70S ribosomes at high Mg2+ concentrations, establishing that L34 facilitates 70S ribosome assembly by functionally substituting for Mg2+. Bacterial genetics (deletion and suppressor mutants), sucrose gradient sedimentation, in vitro subunit association assay, Mg2+ content measurement Journal of bacteriology High 25182490
1989 The primary structure of rat ribosomal protein L34 was determined: it contains 117 amino acids (N-terminal methionine removed post-translationally), has an Mr of 13,498, and is encoded by 7–9 gene copies in the rat genome with an mRNA of ~630 nucleotides. cDNA sequencing, NH2-terminal amino acid sequencing, Southern hybridization FEBS letters Medium 2721685

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Nucleolar proteome dynamics. Nature 934 15635413
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2013 Structures of the human and Drosophila 80S ribosome. Nature 481 23636399
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2004 The molecular mechanics of eukaryotic translation. Annual review of biochemistry 396 15189156
2015 Structure of the human 80S ribosome. Nature 380 25901680
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2003 Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 276 14567916
2018 Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation. Cell reports 274 30110629
1995 Structure and evolution of mammalian ribosomal proteins. Biochemistry and cell biology = Biochimie et biologie cellulaire 265 8722009
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
2014 Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell 221 24725412
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
1976 The sequence determination of a protein in a micro scale: the sequence analysis of ribosomal protein L34 of Escherichia coli. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 146 783033
1982 The nucleotide sequence of the dnaA gene promoter and of the adjacent rpmH gene, coding for the ribosomal protein L34, of Escherichia coli. The EMBO journal 112 6329723
1977 Isolation of eukaryotic ribosomal proteins. Purification and characterization of 60 S ribosomal subunit proteins L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37'. The Journal of biological chemistry 68 863909
2014 Defect in the formation of 70S ribosomes caused by lack of ribosomal protein L34 can be suppressed by magnesium. Journal of bacteriology 54 25182490
2015 Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. Gene 43 26526135
2019 lncRNA RPL34-AS1 inhibits cell proliferation and invasion while promoting apoptosis by competitively binding miR-3663-3p/RGS4 in papillary thyroid cancer. Journal of cellular physiology 37 31587286
2016 Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget 37 27845896
1996 Promoter elements controlling developmental and environmental regulation of a tobacco ribosomal protein gene L34. Plant molecular biology 37 9002604
2022 Lactobacillus rhamnosus L34 attenuates chronic kidney disease progression in a 5/6 nephrectomy mouse model through the excretion of anti-inflammatory molecules. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 32 35138387
2022 Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34. International journal of molecular sciences 29 35269654
2017 Silencing of Ribosomal Protein L34 (RPL34) Inhibits the Proliferation and Invasion of Esophageal Cancer Cells. Oncology research 29 28109079
2015 RNAi-mediated RPL34 knockdown suppresses the growth of human gastric cancer cells. Oncology reports 29 26323242
2018 Knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway. Journal of cellular biochemistry 27 30216512
1999 Identification of ribosomal protein L34 as a novel Cdk5 inhibitor. Biochemical and biophysical research communications 27 10049762
2010 Dystroglycan and mitochondrial ribosomal protein L34 regulate differentiation in the Drosophila eye. PloS one 24 20463973
2021 RPL34-AS1-induced RPL34 inhibits cervical cancer cell tumorigenesis via the MDM2-P53 pathway. Cancer science 22 33675124
2019 RPL34-AS1 functions as tumor suppressive lncRNA in esophageal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 31574377
1995 Relationship of the expression of the S20 and L34 ribosomal proteins to polyamine biosynthesis in Escherichia coli. The international journal of biochemistry & cell biology 21 7539334
2017 Perturbation of the F19-L34 Contact in Amyloid β (1-40) Fibrils Induces Only Local Structural Changes but Abolishes Cytotoxicity. The journal of physical chemistry letters 14 28910107
1984 The primary structure of a gene encoding yeast ribosomal protein L34. Current genetics 14 24173509
2017 Influence of the RPL34 gene on the growth and metastasis of oral squamous cell carcinoma cells. Archives of oral biology 13 28697409
2021 A novel lncRNA, RPL34-AS1, promotes proliferation and angiogenesis in glioma by regulating VEGFA. Journal of Cancer 11 34539892
1999 The ribosomal protein L34 gene from the mosquito, Aedes albopictus: exon-intron organization, copy number, and potential regulatory elements. Insect biochemistry and molecular biology 11 10612044
2022 LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis. BMC cancer 10 36162992
2022 Suppression of RPL34 Inhibits Tumor Cell Proliferation and Promotes Apoptosis in Glioblastoma. Applied biochemistry and biotechnology 9 35377127
2023 Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway. Human gene therapy 7 37427415
1989 The primary structure of rat ribosomal protein L34. FEBS letters 7 2721685
2014 Draft genome sequences and description of Lactobacillus rhamnosus strains L31, L34, and L35. Standards in genomic sciences 6 25197459
1994 Mosquito ribosomal protein rpL31 resembles rat rpL34: cDNA and deduced amino acid sequence. Biochimica et biophysica acta 6 8049275
2022 Long non-coding RNA RPL34-AS1 ameliorates oxygen-glucose deprivation-induced neuronal injury via modulating miR-223-3p/IGF1R axis. Human cell 4 36006565
2019 Knockdown of RPL34 suppresses osteosarcoma cell proliferation likely through EIF3/FAU signaling pathway. Translational cancer research 4 35116824
2018 Bacteriocin Isolated from Lactobacillus Rhamnosus L34 Has Antibacterial Effects in a Rabbit Model of Infection After Mandible Fracture Fixation. Medical science monitor : international medical journal of experimental and clinical research 4 30408016
2018 Summation of peaks and L34 ribosomal protein in the presence and absence of antibiotics enables susceptibility testing using MALDI-TOF mass spectrometry in 2h from Escherichia coli-positive blood cultures. Enfermedades infecciosas y microbiologia clinica (English ed.) 2 30236887
2005 Ribosomal proteins L34 and S29 of amphioxus Branchiostoma belcheri tsingtauense: cDNAs cloning and gene copy number. Acta biochimica Polonica 2 16025162
2003 Sequencing and characterization of the Xenopus laevis ribosomal protein L34 cDNA. Gene 2 14585508
2022 LncRNA RPL34-AS1 sponges miR-3656 to suppress cell proliferation in colorectal cancer. In vitro cellular & developmental biology. Animal 1 35773374
2000 Molecular cloning and complete cDNA sequences of the ribosomal proteins rpl34 and rpl44 from Aedes triseriatus mosquitoes. DNA sequence : the journal of DNA sequencing and mapping 1 11328654
2023 RPL34-Divergent Transcript, a Novel Long NonCoding Ribonucleic Acid, Promotes Migration by Activating Epithelial-Mesenchymal Transition in Glioma. World neurosurgery 0 37689361