Affinage

RPL34

Large ribosomal subunit protein eL34 · UniProt P49207

Length
117 aa
Mass
13.3 kDa
Annotated
2026-06-10
38 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL34 (eL34/L34) is a structural component of the large ribosomal subunit that facilitates ribosome assembly: in Bacillus subtilis its loss causes defective 70S formation and slow growth, and 50S subunits lacking L34 join the small subunit only at elevated Mg2+, demonstrating that L34 promotes subunit association in a manner partially substitutable by Mg2+ (PMID:25182490). Beyond its structural role, L34 carries out extra-ribosomal regulatory functions: it physically associates with and post-translationally inhibits ornithine and arginine decarboxylases to suppress polyamine biosynthesis (PMID:7539334), and it binds and inhibits the kinase activities of p35-activated Cdk5 and Cdk4/cyclin D1 without acting on Cdk2 (PMID:10049762). RPL34 protein stability is controlled by ubiquitination, which is reduced by its physical partner CAND1 (PMID:37427415). Across multiple human cancers, RPL34 supports proliferation and survival and is implicated in cell-cycle progression (PMID:26526135, PMID:26323242), acting through PI3K/Akt (PMID:28109079), JAK/STAT3 and JAK2/STAT3 (PMID:30216512, PMID:37427415), and p53-related signaling (PMID:27845896, PMID:33675124). A parallel role for the distinct mitochondrial ribosomal protein mRpL34 in Drosophila photoreceptor differentiation has also been documented (PMID:20463973).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1995 Medium

    Established the first extra-ribosomal activity of L34 by showing it directly inhibits a metabolic enzyme rather than acting only in translation.

    Evidence Immunoprecipitation and in vivo overexpression with enzyme activity assays in E. coli, with specificity controls against eight other ribosomal proteins

    PMID:7539334

    Open questions at the time
    • Binding interface and stoichiometry with the decarboxylases not defined
    • Whether the same inhibition occurs in eukaryotic cells untested
  2. 1999 Medium

    Identified L34 as a kinase regulator, linking a ribosomal protein to cell-cycle/CDK control.

    Evidence Yeast two-hybrid screen of HeLa cDNA plus in vitro kinase inhibition assays against Cdk5/p35, Cdk4/cyclin D1, and Cdk2/cyclin A

    PMID:10049762

    Open questions at the time
    • No in-cell validation of CDK inhibition
    • Structural basis of selectivity for Cdk5/Cdk4 over Cdk2 unknown
  3. 2010 Medium

    Demonstrated a cell-autonomous developmental requirement for the mitochondrial ribosomal protein mRpL34 in tissue differentiation.

    Evidence Drosophila genetic deficiency analysis with transgenic rescue and immunohistochemistry of the eye

    PMID:20463973

    Open questions at the time
    • mRpL34 is a distinct mitochondrial protein, not cytoplasmic RPL34
    • Molecular mechanism linking mito-ribosome function to photoreceptor differentiation not resolved
  4. 2014 High

    Defined the core structural function of L34, showing it promotes large-small subunit joining and that Mg2+ can partially substitute for it.

    Evidence rpmH deletion, suppressor mutant analysis altering intracellular Mg2+, and in vitro subunit association reconstitution in B. subtilis

    PMID:25182490

    Open questions at the time
    • Mechanism by which L34 stabilizes the subunit interface at the residue level not shown
    • Generalization to eukaryotic 80S assembly not tested here
  5. 2015 Low

    Connected RPL34 to cancer cell proliferation and survival, framing it as a candidate proliferation driver.

    Evidence Lentiviral shRNA/siRNA knockdown in NSCLC (H1299) and gastric (SGC-7901) cells with proliferation, apoptosis, and flow-cytometry cell-cycle readouts

    PMID:26323242 PMID:26526135

    Open questions at the time
    • No pathway mechanism established
    • Knockdown phenotypes could reflect general loss of ribosome function rather than a specific role
  6. 2018 Low

    Began placing RPL34 phenotypes onto named signaling axes across tumor types.

    Evidence shRNA knockdown with downstream western blots for p-PI3K/p-Akt (esophageal), p-JAK/p-STAT3 (glioma), and MAPK/p53 expression profiling (pancreatic), plus xenograft assays

    PMID:27845896 PMID:28109079 PMID:30216512

    Open questions at the time
    • Pathway changes are correlative downstream of knockdown, not direct
    • No demonstration of direct molecular coupling between RPL34 and these kinases
  7. 2022 Medium

    Identified a protein partner controlling RPL34 abundance and tied it to STAT3 signaling, providing the first regulatory mechanism for RPL34 protein levels.

    Evidence Co-IP identification of CAND1, ubiquitination assays showing CAND1 reduces RPL34 ubiquitination, and JAK2/STAT3 western blots in colorectal cancer cells

    PMID:37427415

    Open questions at the time
    • E3 ligase acting on RPL34 not identified
    • Direct vs. indirect CAND1-RPL34 interaction and ubiquitin site mapping not resolved
  8. 2022 Low

    Extended RPL34 effector linkage to apoptotic machinery and a tumor-suppressor context, indicating context-dependent roles.

    Evidence shRNA knockdown with Bad/Caspase7/PARP western blots in glioblastoma; MDM2-p53 pharmacologic modulation and RPL34-AS1 lncRNA RIP assays in cervical cancer

    PMID:33675124 PMID:35116824 PMID:35377127

    Open questions at the time
    • Opposing oncogenic vs tumor-suppressor roles across tissues unreconciled
    • Effector pathways inferred from expression/western readouts, not reconstituted

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPL34's structural ribosomal role mechanistically relates to its diverse extra-ribosomal activities (CDK inhibition, decarboxylase inhibition, signaling control) remains unresolved.
  • No structure of RPL34 bound to any extra-ribosomal partner
  • Whether free vs ribosome-bound RPL34 mediates signaling effects unknown
  • Direct molecular link between RPL34 and PI3K/Akt or JAK/STAT pathways not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005840 ribosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 1
Partners
CAND1CDK4CDK5
Complex memberships
60S/large ribosomal subunit

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RPL34 (60S ribosomal protein L34) was identified as a Cdk5-interacting protein via yeast two-hybrid screening 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. L34 does not interact with Cdk2 in the two-hybrid assay and does not inhibit Cdk2/cyclin A enzyme activity. Yeast two-hybrid screening, biochemical kinase inhibition assays Biochemical and biophysical research communications Medium 10049762
1995 Ribosomal protein L34 (and S20) physically interact with ornithine decarboxylase and arginine decarboxylase (shown by immunoprecipitation), and in vivo overexpression of L34 specifically inhibits these enzymes and reduces total polyamine biosynthesis in E. coli through reversible post-translational inhibition. The effect was specific: overexpression of eight other ribosomal proteins had no influence. Immunoprecipitation, in vivo overexpression, enzyme activity assays The international journal of biochemistry & cell biology Medium 7539334
2014 In Bacillus subtilis, deletion of rpmH (encoding ribosomal protein L34) causes a severe slow-growth phenotype and defective 70S ribosome formation. Suppressor mutations that increase intracellular Mg2+ (disruption of yhdP Mg2+-efflux gene or overexpression of mgtE Mg2+-importer) rescue both growth and 70S assembly. In vitro subunit association experiments demonstrated that 50S subunits lacking L34 can form 70S ribosomes only at high Mg2+ concentration, showing that L34 facilitates 70S ribosome assembly and that this function can be partially replaced by Mg2+. Genetic deletion, suppressor mutant characterization, in vitro subunit association assay, Mg2+ quantification Journal of bacteriology High 25182490
2015 Lentivirus-mediated shRNA knockdown of RPL34 in human NSCLC cell line H1299 caused a strong decrease in proliferation, moderate but significant increase in apoptosis, and S-phase cell cycle arrest, establishing that RPL34 is required for normal cell cycle progression and survival in NSCLC cells. Lentivirus-mediated shRNA knockdown, flow cytometry, cell proliferation and colony formation assays Gene Low 26526135
2015 RNAi-mediated knockdown of RPL34 in human gastric cancer cell line SGC-7901 significantly suppressed cell proliferation, increased apoptosis, and arrested cells in S phase, demonstrating a role for RPL34 in cell cycle progression and survival in gastric cancer cells. Lentivirus-mediated siRNA knockdown, cell proliferation assay, flow cytometry Oncology reports Low 26323242
2016 Knockdown of RPL34 in pancreatic cancer cells suppresses proliferation, colony formation, migration, and drug resistance, accompanied by G2 phase arrest and apoptosis. Gene expression profiling following RPL34 silencing revealed alteration of the MAPK and p53 signaling pathways. RPL34 overexpression is correlated with decreased methylation of its promoter in pancreatic cancer. shRNA knockdown, gene expression profiling, in vivo xenograft assay Oncotarget Low 27845896
2017 Knockdown of RPL34 in esophageal cancer cells inhibited proliferation, migration, and invasion, and significantly downregulated protein levels of p-PI3K and p-Akt, indicating that RPL34 promotes esophageal cancer cell proliferation and invasion at least in part through the PI3K/Akt signaling pathway. shRNA knockdown, western blot for p-PI3K/p-Akt, in vivo tumor growth assay Oncology research Low 28109079
2018 Knockdown of RPL34 in human glioma cells markedly inhibited proliferation, migration, and invasion, and prevented epithelial-mesenchymal transition. Mechanistic analysis showed that knockdown of RPL34 significantly downregulated levels of p-JAK and p-STAT3, indicating RPL34 promotes glioma cell proliferation and migration through activation of the JAK/STAT3 signaling pathway. shRNA knockdown, western blot for p-JAK/p-STAT3, proliferation/migration/invasion assays Journal of cellular biochemistry Low 30216512
2021 RPL34 acts as a tumor suppressor in cervical cancer and regulates tumorigenesis through the MDM2-P53 pathway, as validated by use of actinomycin D, MDM2 inhibitor, and western blotting assays. Additionally, the antisense lncRNA RPL34-AS1 regulates RPL34 expression, and RPL34 can reverse the oncogenic effect of RPL34-AS1 in cervical cancer cells. Western blot with MDM2 inhibitor and actinomycin D treatment, overexpression and knockdown, RIP assay Cancer science Low 33675124
2022 RPL34 interacts with CAND1 (cullin-associated NEDD8-dissociated protein 1), a negative regulator of cullin-RING ligases, as identified by immunoprecipitation assays in colorectal cancer cells. CAND1 overexpression reduced ubiquitination of RPL34 and stabilized RPL34 protein. RPL34 promotes CRC proliferation, migration, and EMT through activation of the JAK2/STAT3 signaling pathway. Immunoprecipitation assay, overexpression/knockdown, ubiquitination assay, western blot for JAK2/STAT3 Human gene therapy Medium 37427415
2022 Knockdown of RPL34 in glioblastoma cells inhibited tumor cell proliferation and induced apoptosis through activation of the Bad/Caspase7/PARP signaling pathway. shRNA knockdown, apoptosis signaling western blot (Bad, Caspase7, PARP), cell proliferation assay Applied biochemistry and biotechnology Low 35377127
2019 Knockdown of RPL34 in osteosarcoma cells (Saos-2) suppressed cell proliferation and was accompanied by downregulation of EIF3A and EIF3F and upregulation of FAU at the mRNA level, suggesting RPL34 may act on cell proliferation through EIF3/FAU signaling. shRNA knockdown, qRT-PCR for EIF3A, EIF3F, EIF3G, UBA52, UBC, FAU; western blot Translational cancer research Low 35116824
2010 In Drosophila, loss of the mitochondrial ribosomal gene mRpL34 (neighboring Dystroglycan) causes severely disrupted photoreceptor (R) cells, lens, and ommatidia in the adult eye, and expression of an mRpL34 transgene rescues much of this differentiation phenotype, establishing a cell-autonomous role for mRpL34 in R cell differentiation in the pupa. Genetic rescue with transgene, deficiency line analysis, immunohistochemistry PloS one Medium 20463973

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 55 25182490
2015 Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. Gene 44 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
1996 Promoter elements controlling developmental and environmental regulation of a tobacco ribosomal protein gene L34. Plant molecular biology 37 9002604
2016 Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget 36 27845896
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 33 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 31 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 12 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
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 5 30408016
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 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

Missed literature

Know a paper Affinage missed for RPL34? Flag it for the maintainers and the community.

No submissions yet.