Affinage

RPS6

Small ribosomal subunit protein eS6 · UniProt P62753

Length
249 aa
Mass
28.7 kDa
Annotated
2026-06-10
93 papers in source corpus 31 papers cited in narrative 32 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

RPS6 is a core structural protein of the 40S small ribosomal subunit whose phosphorylation at clustered C-terminal serines (Ser235/236, Ser240/244) integrates multiple upstream kinase inputs to tune translation and an expanding set of physiological processes (PMID:22948214, PMID:30969964, PMID:36474017). Its phosphorylation is driven convergently by mTORC1/p70S6K, ERK1/2-RSK/p90RSK, PKA, and CK2, with distinct kinases coupling distinct stimuli to RPS6: RSK/p90S6K relays growth-factor, cytokine (IL-3), and preconditioning signals (PMID:37068088, PMID:26276876, PMID:32550912), ERK1/2 selectively enhances translation of mRNAs bearing AU-rich proximal UTR elements such as CXCL8 and TNFAIP6 (PMID:30969964), and CK2 provides an mTOR/ERK-independent route in drug-resistant tumor cells (PMID:26919095); β-arrestins scaffold a constitutive p70S6K/rpS6 complex through which FSH/GPCR signaling drives phosphorylation and 5'TOP mRNA translation (PMID:29084767). The phosphorylation state is held in check by phosphatase activity, with PP2A-PPP2R5D acting as a brake on mTORC1-RPS6 signaling (PMID:37572851). Notably, RPS6 phosphorylation is neither sufficient nor necessary for translational activation of TOP mRNAs, which instead depends on PI3-kinase/PKB signaling (PMID:11713299, PMID:12417714). Beyond translation, phospho-RPS6 functions as a context-dependent modulator of tissue remodeling: it disrupts the Sertoli-cell blood-testis barrier and spermatogenesis by remodeling actin and microtubule cytoskeletons through an Akt-MMP-9 axis and altered Arp3/N-WASP-driven actin debundling (PMID:22948214, PMID:25217631, PMID:25714812, PMID:29089336), and it is required for peripheral and central axon regeneration and for proper skin wound closure (PMID:37068088, PMID:37098351). RPS6 dosage is critical in vivo: hepatic Rps6 insufficiency causes failed bile duct development and hepatocyte loss in a partially p53-dependent manner (PMID:36656901), and heterozygous Rps6 deletion produces a Diamond-Blackfan-like macrocytic anemia (PMID:22198155). RPS6 also engages non-ribosomal partners, interacting with spliceosome components and binding MCM7 to regulate its alternative splicing and oncogenic activity, while its protein homeostasis is controlled by NBEAL2 (PMID:39309509, PMID:38272677).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Defining the human RPS6 gene structure established the locus and revealed a TATA-less, CpG-island promoter initiating within an oligopyrimidine tract, framing RPS6 as a housekeeping ribosomal gene.

    Evidence PCR cloning, sequencing, primer extension, and FISH mapping to 9p21

    PMID:1301164

    Open questions at the time
    • No functional consequence of the 5'TOP promoter element established
    • Does not address protein function or phosphoregulation
  2. 2002 High

    Genetic and pharmacological dissection answered whether RPS6 phosphorylation drives the classic TOP mRNA translation response, showing it is neither necessary nor sufficient and that PI3K/PKB integrity is the controlling input.

    Evidence Dominant-negative/constitutively active PI3K-PDK1-PKB mutants, S6K1-null ES cells, rapamycin, polysome profiling

    PMID:11713299 PMID:12417714

    Open questions at the time
    • Does not identify the true PI3K-dependent effector for TOP mRNA translation
    • Leaves the functional purpose of RPS6 phosphorylation unresolved
  3. 2006 Medium

    Yeast paralog genetics linked rpS6 dosage to ribosome subunit stoichiometry, cell size, and replicative lifespan, implicating RPS6 levels in translational capacity and aging.

    Evidence Yeast RPS6A/RPS6B deletion strains, polysome profiling, lifespan and cell-size assays; earlier rpL10 genetic interaction with rpS6 in subunit joining

    PMID:15556089 PMID:17174052

    Open questions at the time
    • Ortholog system may not transfer to mammalian RPS6
    • No molecular mechanism connecting dosage to lifespan
  4. 2011 Medium

    A heterozygous Rps6 mouse answered whether RPS6 haploinsufficiency phenocopies ribosomopathies, producing a Diamond-Blackfan/5q--like macrocytic anemia rescued by lenalidomide.

    Evidence Rps6 hemizygous mice, hematopoietic phenotyping, lenalidomide treatment

    PMID:22198155

    Open questions at the time
    • No molecular mechanism for the erythroid defect
    • Single study without human genetic corroboration in the corpus
  5. 2017 High

    A series of phosphomimetic and silencing studies in Sertoli cells and rat testes defined phospho-RPS6 as a cytoskeletal regulator of the blood-testis barrier, acting via Akt-MMP-9 and Arp3/N-WASP actin remodeling.

    Evidence Quadruple phosphomimetic rpS6 mutant, siRNA/shRNA, MMP-9 inhibitor, Akt RNAi, Arp3/N-WASP co-IP, in vivo testis transfection, permeability assays

    PMID:22948214 PMID:25217631 PMID:25714812 PMID:29089336

    Open questions at the time
    • Mechanism connecting ribosomal RPS6 phosphorylation to cytoskeletal effectors not biochemically resolved
    • Phosphomimetic overexpression may not equal endogenous phosphostate
  6. 2018 High

    Identifying a constitutive β-arrestin/p70S6K/rpS6 complex answered how GPCR (FSHR) signaling delivers phosphorylation to RPS6, defining a scaffolded route to 5'TOP mRNA translation.

    Evidence Reciprocal co-IP, β-arrestin and Gαs depletion, computational docking with interface validation, TOP reporter assays in HEK293 and Sertoli cells

    PMID:29084767

    Open questions at the time
    • Interface defined for β-arrestin1/p70S6K, not directly for RPS6
    • Generality across other GPCRs untested
  7. 2019 Medium

    Reporter and pathway studies clarified the translational output of RPS6 phosphorylation, showing ERK1/2-driven Ser235/236 phosphorylation selectively enhances translation of AU-rich proximal-UTR mRNAs.

    Evidence UTR Nanoluc reporters with mutagenesis, ERK1/2 inhibitors, polyribosome analysis in macrophages and A549 cells

    PMID:30969964

    Open questions at the time
    • Direct RPS6 contact with the APS element not demonstrated
    • Single lab, limited transcript set
  8. 2020 Medium

    Kinase-specific studies extended the RSK-RPS6 axis to tissue regeneration and proliferation, with RSK-3 driving cartilage progenitor proliferation and IL-3/p90S6K driving eosinophil translational programs.

    Evidence RSK-3 knockout/overexpression in OA mice, CSPC profiling; eosinophil p90S6K inhibition with semaphorin-7A translation readout

    PMID:26276876 PMID:32550912

    Open questions at the time
    • RPS6 phosphorylation inferred as the effective downstream node but not isolated genetically in these contexts
    • Single study per tissue
  9. 2023 High

    Non-phosphorylatable RPS6 knock-in mice resolved whether RPS6 phosphorylation is functionally required in vivo, showing it is essential for PNS/CNS axon regeneration (downstream of RSK2) and a modulator of skin wound closure.

    Evidence Non-phosphorylatable RPS6 knock-in, RSK2 KO/overexpression, DRG preconditioning, dorsal column crush, wound healing assays, behavioral recovery

    PMID:37068088 PMID:37098351

    Open questions at the time
    • Molecular targets through which phospho-RPS6 acts in neurons and skin not defined
    • Distinction between ribosomal and extra-ribosomal action unresolved
  10. 2023 High

    Disease-model genetics defined RPS6 regulation and dosage requirements: PPP2R5D-PP2A is a phosphatase brake on mTORC1-RPS6, and hepatic Rps6 insufficiency causes biliary and hepatocyte failure that is only partially p53-dependent.

    Evidence CRISPR-PRIME PPP2R5D variant cell lines with phosphoproteomics and inhibitors; liver-specific Rps6 KO with c-Myc/p53 rescue and epistasis

    PMID:36656901 PMID:37572851

    Open questions at the time
    • p53-independent component of the liver phenotype unidentified
    • Whether PP2A directly dephosphorylates RPS6 versus upstream kinases not separated
  11. 2024 Medium

    Interactome studies revealed non-ribosomal RPS6 functions, binding spliceosome components and MCM7 to regulate alternative splicing and oncogenic activity, with NBEAL2 controlling RPS6 protein homeostasis.

    Evidence IP-MS, RIP-seq, RNA-seq, xenografts, vivo-PMO knockdown; NBEAL2 co-IP and CRISPR KO in mast cells

    PMID:38272677 PMID:39309509

    Open questions at the time
    • Direct versus ribosome-mediated splicing role not fully separated
    • Structural basis of MCM7 and NBEAL2 binding only predicted
  12. 2025 Medium

    Newer studies broaden RPS6 biology to intercellular transfer and immune signaling, with astrocyte EV-packaged Rps6 supporting axonal local translation and histamine-H2R driving RPS6 phosphorylation in dendritic cells.

    Evidence Astrocyte EV proteomics and vesicular Rps6 knockdown with local translation/synaptic readouts; whole-blood basophil/H2R antagonist flow cytometry

    PMID:40932794 PMID:41416952

    Open questions at the time
    • Mechanism of RPS6 EV packaging and uptake unknown
    • Functional downstream targets of H2R-RPS6 in DCs undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPS6 phosphorylation at specific serines mechanistically translates into selective mRNA translation and into its diverse extra-ribosomal effects on cytoskeleton, splicing, and tissue remodeling remains unresolved.
  • No structural model linking phospho-state to ribosome function or partner binding
  • Whether cytoskeletal and splicing roles require ribosome association is unknown
  • Substrate specificity differences among S6K1, RSK, CK2 inputs not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0045182 translation regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 1
Partners
ARP3ARRB1MCM7NBEAL2PPP2R5DRPS4XLRPS6KB1RSK2
Complex memberships
40S ribosomal subunitspliceosome (associated)β-arrestin/p70S6K/rpS6 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Neither phosphorylation of rpS6 nor activation of S6K1 is sufficient or necessary for translational activation of TOP mRNAs; amino acid-dependent translational regulation of TOP mRNAs is fully dependent on PI3-kinase signaling but does not require S6K1 activity or rpS6 phosphorylation, as shown in S6K1-null ES cells and with dominant-negative S6K1 mutants. Dominant-negative S6K1 overexpression, S6K1 knockout ES cells, PI3-kinase inhibitor (LY294002), rapamycin treatment, polysome analysis Molecular and cellular biology High 11713299
2002 Translation of TOP mRNAs by growth and mitogenic signals requires PI3-kinase/PKB pathway integrity but neither rpS6 phosphorylation nor S6K1 activity; constitutively active PKBα relieves translational repression in quiescent cells, while complete S6K1/rpS6 inhibition by rapamycin has only mild repressive effects on TOP mRNA translation. Overexpression of constitutively active and dominant-negative PI3K/PDK1/PKBα mutants, PTEN overexpression, rapamycin treatment, polysome analysis, S6K1-null ES cells Molecular and cellular biology High 12417714
1992 The human RPS6 gene is located at chromosome 9p21, spans 3979 bp, comprises six exons, lacks a consensus TATA box, initiates transcription from a single C residue within an 11 bp oligopyrimidine tract, and the 5' region has features of a CpG-rich island. PCR-based cloning, DNA sequencing, primer extension analysis, fluorescence in situ hybridization (FISH) Human molecular genetics High 1301164
2012 Phosphorylated rpS6 (activated by mTORC1) disrupts the Sertoli cell tight junction permeability barrier and blood-testis barrier integrity by reorganizing F-actin from a bundled to debundled configuration and altering recruitment of adhesion proteins (claudin-11, occludin) at the BTB; rpS6 silencing by siRNA/shRNA promotes barrier tightening. Constitutively active quadruple phosphomimetic rpS6 mutant (S235E/S236E/S240E/S244E) overexpression in Sertoli cells, siRNA/shRNA knockdown, tight junction permeability assay, immunofluorescence Endocrinology High 22948214
2014 Phosphorylated rpS6 disrupts blood-testis barrier function via an Akt-MMP-9 axis: constitutively active p-rpS6 abolishes Akt phosphorylation, induces MMP-9 secretion, and MMP-9 proteolytically degrades tight junction proteins at the BTB; a specific MMP-9 inhibitor blocks this disruption, and Akt siRNA knockdown mimics p-rpS6 mutant effects. Constitutively active rpS6 phosphomimetic mutant overexpression, MMP-9 specific inhibitor, Akt RNAi knockdown, tight junction permeability assay, immunoblotting Journal of cell science High 25217631
2015 Phosphorylated rpS6 disrupts Sertoli cell BTB tight junction permeability by redistributing activated Arp3 and altering Arp3-N-WASP interaction, converting actin microfilaments from bundled to unbundled/branched configuration; Akt knockdown mimics this phenotype, placing Akt downstream of p-rpS6 in this pathway. Constitutively active rpS6 phosphomimetic mutant overexpression, site-directed mutagenesis, Akt RNAi, Arp3/N-WASP co-immunoprecipitation, F-actin bundling assay, tight junction permeability assay Endocrinology High 25714812
2017 Overexpression of wild-type rpS6 and a constitutively active quadruple phosphomimetic rpS6 mutant in rat testes in vivo disrupts BTB integrity and impairs spermatogenesis (loss of spermatid polarity, germ cell exfoliation) by reorganizing actin- and microtubule-based cytoskeletons through altered spatiotemporal expression of actin- and MT-binding/regulatory proteins. In vivo transfection of rat testes with rpS6-WT and p-rpS6-MT plasmids using jet-PEI reagent, in vivo BTB integrity assay, immunofluorescence, immunoblotting American journal of physiology. Endocrinology and metabolism High 29089336
2023 RPS6 phosphorylation is essential for both PNS and CNS axon regeneration in mice; this phosphorylation is induced during the preconditioning effect in DRG neurons and is controlled by the p90S6 kinase RSK2; RSK2 controls the preconditioning effect, and the RSK2-RPS6 axis promotes CNS regeneration, spinal cord synaptic plasticity, and functional recovery. Mouse genetic models (knock-in non-phosphorylatable RPS6, RSK2 knockout/overexpression), DRG neuron preconditioning, dorsal column crush injury, immunofluorescence, behavioral assays PLoS biology High 37068088
2023 Phosphorylation of rpS6 forms a spatially defined zone surrounding skin wounds within minutes of injury, persisting until healing is complete; a mouse model unable to phosphorylate rpS6 shows initial acceleration but ultimately impaired wound closure, identifying p-rpS6 as a modulator of the healing process rather than its driver. Knock-in non-phosphorylatable rpS6 mouse model, wound healing assays, immunofluorescence for p-rpS6, live imaging Developmental cell High 37098351
2011 Heterozygous deletion of one Rps6 allele in mice produces a hypoproliferative macrocytic anemia similar to Diamond-Blackfan anemia and the 5q- syndrome, demonstrating that ribosomal protein S6 haploinsufficiency impairs erythropoiesis; lenalidomide therapy improves this anemia. Rps6 hemizygous mouse model, hematopoietic phenotyping, lenalidomide treatment Experimental hematology Medium 22198155
2023 PPP2R5D pathogenic variants (E198K, E420K) cause RPS6 hyperphosphorylation via converging mTORC1/p70S6K signaling cascades; rapamycin or RPS6-kinase inhibitor (LY2584702) suppresses this hyperphosphorylation, indicating PP2A-PPP2R5D normally acts as a phosphatase brake on mTORC1-RPS6 signaling. CRISPR-PRIME editing to generate heterozygous PPP2R5D variant cell lines, quantitative phosphoproteomics, rapamycin and kinase inhibitor treatment, immunoblotting The Journal of biological chemistry High 37572851
2018 β-arrestins constitutively assemble a p70S6K/rpS6 complex in HEK293 cells and primary Sertoli cells; this interaction is direct with a defined interface between β-arrestin 1 and p70S6K; upon FSH/FSHR stimulation, G protein-dependent signaling enhances p70S6K activity within this preassembled β-arrestin/p70S6K/rpS6 complex, leading to rpS6 phosphorylation and 5'TOP mRNA translation. Co-immunoprecipitation, β-arrestin depletion, Gαs-depleted cells, computational docking with experimental interface validation, 5'TOP mRNA translation reporter assays FASEB journal High 29084767
2015 IL-3, unlike GM-CSF or IL-5, triggers prolonged phosphorylation of RPS6 via activation of the upstream kinase p90S6K (RSK); blockade of p90S6K inhibits RPS6 phosphorylation and IL-3-enhanced semaphorin-7A translation in human eosinophils, establishing a p90S6K-RPS6 axis for IL-3-specific translational control. Human peripheral blood eosinophil stimulation, p90S6K inhibitor treatment, immunoblotting for p-RPS6 and p-p90S6K, protein synthesis measurements Journal of immunology Medium 26276876
2019 RPS6 p.R232H somatic variant overexpressed in animal models promotes increased cell proliferation (distinct from the MTOR p.S2215F variant which causes neuronal migration delay and cytomegaly); double mutants show synergistic effects with increased proliferation, migration defects, cytomegalic cells with eccentric nuclei and binucleation. Overexpression of RPS6 p.R232H and MTOR p.S2215F variants in animal models (in utero electroporation/mouse), phenotypic analysis of neuronal migration and cell morphology Human molecular genetics Medium 31411685
2015 Blocking rpS6 phosphorylation (non-phosphorylatable rpS6 knock-in) in Tsc1-deleted kidneys exacerbates cystogenesis and causes severe nephron damage, renal fibrosis, and kidney failure, revealing that phosphorylated rpS6 normally suppresses cystogenesis and fibrosis in the context of hyperactive mTORC1; this is associated with persistent mTORC1 activation and accumulation of hyperphosphorylated 4E-BP1. Non-phosphorylatable rpS6 knock-in crossed with renal proximal tubule-specific Tsc1 knockout mice, rapamycin treatment, immunoblotting, histology, kidney function assays Journal of the American Society of Nephrology High 26296742
2021 RPS6 expression (active protein synthesis marker) is present in senescent cells but absent in quiescent cells, enabling discrimination between quiescence and senescence states; combined use of Ki67, RPS6, and beta-galactosidase identifies transitional G0 states including G0-entry, G0, G0-alert, and early/late senescence. Immunofluorescence for RPS6, Ki67, and beta-galactosidase activity in primary cell cultures under defined quiescence-inducing and genotoxic stress conditions International journal of molecular sciences Medium 33803589
2004 Yeast rpL10/Grc5p (LSU) functionally interacts with the SSU protein rpS6 in ribosomal subunit joining and modulation of differential protein expression, and interacts with nuclear export factor Nmd3p to modulate the cellular polysome complement. Genetic interaction analysis, polysome profiling, protein expression analysis in yeast deletion strains FEMS yeast research Medium 15556089
2006 Deletion of the SSU RPS6B paralog (but not RPS6A) in yeast increases replicative life span by 45% and produces a large shift in free ribosomal subunit stoichiometry and reduced cell size, implicating rpS6 dosage in translational regulation and aging. Yeast paralog deletion strains, replicative lifespan assay, polysome/subunit profiling, cell size measurement Experimental gerontology Medium 17174052
2019 rpS6 phosphorylation (Ser235/236) enhances translation of mRNAs containing AU-rich proximal UTR sequences (APS), including CXCL8 and TNFAIP6; this is triggered by ERK1/2 signaling in macrophages and is attenuated by ERK1/2 inhibitors; induction via TAK1, Akt, or PKA signaling in A549 cells also enhances APS-reporter translation. UTR reporter assays (Nanoluc), site-directed mutagenesis of UTR, ERK1/2 inhibitors, polyribosome analysis, phospho-rpS6 immunoblotting PLoS genetics Medium 30969964
2023 Hepatic Rps6 insufficiency (conditional deletion) causes failed bile duct development and loss of hepatocyte viability; this phenotype is partially p53-dependent; overexpression of c-Myc ameliorates while a hyperstable p53 mutant partially recapitulates specific hepatopathies; co-deletion of p53 fails to restore biliary development, indicating additional p53-independent mechanisms. Liver-specific Rps6 conditional knockout mice, c-Myc overexpression, p53 mutant overexpression, p53 co-deletion, histology, bile duct morphology analysis PLoS genetics High 36656901
2024 RPS6 interacts with spliceosome complex proteins (identified by immunoprecipitation-mass spectrometry) and regulates alternative splicing events; specifically, RPS6 binds MCM7 and regulates its alternative splicing to increase oncogenic activity; RPS6 depletion also affects cell cycle and DNA replication pathways beyond its ribosomal function. Immunoprecipitation followed by mass spectrometry, RNA-seq, proteomics, RNA immunoprecipitation sequencing (RIP-seq), xenograft models, vivo-PMO knockdown Acta pharmaceutica sinica. B Medium 39309509
2024 NBEAL2 interacts with RPS6 (identified by co-immunoprecipitation); NBEAL2/RPS6 complex formation controls RPS6 protein homeostasis in mast cells; NBEAL2 inactivation leads to accumulation of strongly p90RSK-phosphorylated RPS6, resulting in abnormal mast cell phenotype with prolonged growth factor-independent survival and pro-inflammatory activity. Co-immunoprecipitation, CRISPR/Cas9 knockout, western blotting, flow cytometry, structural prediction (RoseTTAFold) Immunology Medium 38272677
2021 The lnc-Rps4l-encoded peptide RPS4XL interacts with RPS6 (identified by co-immunoprecipitation and mass spectrometry) and inhibits RPS6 phosphorylation at Ser240/Ser244, thereby inhibiting proliferation of pulmonary artery smooth muscle cells under hypoxic conditions. Co-immunoprecipitation, mass spectrometry, immunofluorescence, MTT/BrdU proliferation assays, siRNA knockdown Molecular therapy Medium 33429084
2020 RSK-3 activates rpS6 to accelerate cartilage stem/progenitor cell (CSPC) proliferation; RSK-3 expression positively correlates with cartilage repair capacity; RSK-3 inhibition or deficiency reduces CSPC proliferation and aggravates cartilage damage in OA mice, while RSK-3 enhancement attenuates cartilage injury. RSK-3 knockout mice and chemical inhibition, RSK-3 overexpression, transcriptional profiling of CSPC, in vivo OA mouse models, phospho-rpS6 immunoblotting Theranostics Medium 32550912
2021 RPS6 localized to the 40S small ribosomal subunit functions as a pro-viral host factor for tomato spotted wilt orthotospovirus (TSWV) infectivity; VIGS silencing of the RPS6 gene family in Nicotiana benthamiana confers nearly complete resistance to TSWV. Virus-induced gene silencing (VIGS) screen, TRV-based silencing, TSWV infection assay Molecular plant pathology Medium 34913556
2025 Astrocyte-derived extracellular vesicles containing Rps6 (released in response to amyloid-β) are delivered to axons and enhance local protein synthesis and synaptic integrity in neurons; genetic downregulation of vesicular Rps6 reduces translational regulation in axons and impairs synaptic integrity, demonstrating a glia-to-neuron communication mechanism via EV-packaged RPS6. Primary neuronal/astrocyte cultures, astrocyte EV isolation, proteomics, western blotting, siRNA knockdown of vesicular Rps6, local translation assays, synaptic marker analysis Journal of extracellular vesicles Medium 41416952
2025 p60-S6K1, a shorter isoform of S6K1, promotes RPS6 phosphorylation independently of p60-S6K1's own phosphorylation during recovery from skeletal muscle disuse atrophy; p60-S6K1 upregulation is transcribed from a p60-S6K1-specific transcript (distinct from the full-length S6K1 transcript) and is required for rapid recovery from disuse atrophy. Tail suspension/reloading in WKY and SHRSP rats, immunoblotting for p-RPS6 and p-S6K1 isoforms, RT-PCR for p60-S6K1-specific transcript Laboratory animal research Low 40931334
2021 RPS6 is expressed in the senescent cell state but absent in quiescent cells, identifying RPS6 as a marker of active protein synthesis that distinguishes senescence from quiescence. Immunofluorescence analysis of RPS6 expression across defined G0 states International journal of molecular sciences Low 33803589
2022 Leucine ingestion promotes mTOR translocation to the cell periphery and enhances RPS6 phosphorylation (Ser240/244) in both total and peripheral regions of human skeletal muscle fibers; peripheral p-RPS6 intensity at 60 min positively correlates with myofibrillar protein synthesis rates, linking peripheral mTOR-RPS6 activation to muscle protein synthesis. Human clinical trial with muscle biopsies, immunofluorescence for p-RPS6 and mTOR, mTOR-lysosome co-localization, correlation with myofibrillar protein synthesis rates Amino acids Medium 36474017
2021 RPS6 phosphorylation occurs to a greater extent in the periphery of human skeletal muscle fibers (near focal adhesion complexes marked by paxillin) following anabolic stimuli (feeding and/or resistance exercise); peripheral p-RPS6Ser240/244 phosphorylation is greater after combined exercise+feeding vs. feeding alone. Human muscle biopsies, immunofluorescence for p-RPS6 and paxillin (focal adhesion marker), immunoblotting, region-specific quantification American journal of physiology. Cell physiology Medium 34852208
2025 Histamine released by IgE-dependent basophil degranulation induces RPS6 phosphorylation in plasmacytoid DCs and conventional DCs via histamine receptor 2 (H2R) signaling; this pathway is upstream of RPS6 phosphorylation in the allergic response context. Whole blood stimulation with peanut extract or anti-IgE antibodies, in vitro basophil depletion, histamine receptor antagonists, flow cytometry for p-RPS6 JCI insight Medium 40932794
2016 Protein kinase CK2 mediates a novel pathway of rpS6 phosphorylation in imatinib-resistant CML cells that is independent of MEK/ERK1/2 and PI3K/Akt/mTOR pathways; CK2 inhibition (CX-5011) or CK2 subunit silencing selectively reduces rpS6 phosphorylation and protein synthesis without affecting upstream kinases, indicating CK2 as a direct or parallel regulator of rpS6 phosphorylation. CK2 inhibitor (CX-5011), CK2 subunit siRNA knockdown, immunoblotting for p-rpS6, protein synthesis assays, synergy analysis with imatinib and U0126 Oncotarget Medium 26919095

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 499 21147110
2001 Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin, and is independent of S6K1 and rpS6 phosphorylation. Molecular and cellular biology 236 11713299
2002 Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Molecular and cellular biology 187 12417714
2006 Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span. Experimental gerontology 99 17174052
2013 Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway. Biology of reproduction 89 23486913
2009 Resistance to the Pseudomonas syringae effector HopA1 is governed by the TIR-NBS-LRR protein RPS6 and is enhanced by mutations in SRFR1. Plant physiology 87 19525323
2015 Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway. PloS one 85 25659153
2014 rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9. Journal of cell science 82 25217631
2014 4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N-Ras proto-oncogenes in mice. Hepatology (Baltimore, Md.) 73 25145583
2021 Different Stages of Quiescence, Senescence, and Cell Stress Identified by Molecular Algorithm Based on the Expression of Ki67, RPS6, and Beta-Galactosidase Activity. International journal of molecular sciences 69 33803589
2012 rpS6 Regulates blood-testis barrier dynamics by affecting F-actin organization and protein recruitment. Endocrinology 69 22948214
2010 Select nutrients in the ovine uterine lumen. VIII. Arginine stimulates proliferation of ovine trophectoderm cells through MTOR-RPS6K-RPS6 signaling cascade and synthesis of nitric oxide and polyamines. Biology of reproduction 68 20844281
2015 rpS6 regulates blood-testis barrier dynamics through Arp3-mediated actin microfilament organization in rat sertoli cells. An in vitro study. Endocrinology 66 25714812
2008 Resistance exercise decreases eIF2Bepsilon phosphorylation and potentiates the feeding-induced stimulation of p70S6K1 and rpS6 in young men. American journal of physiology. Regulatory, integrative and comparative physiology 64 18565837
2018 NRF2 through RPS6 Activation Is Related to Anti-HER2 Drug Resistance in HER2-Amplified Gastric Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 62 30504425
2010 Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. Cancer research 62 20959493
2010 Different domains of Phytophthora sojae effector Avr4/6 are recognized by soybean resistance genes Rps4 and Rps6. Molecular plant-microbe interactions : MPMI 55 20192830
2014 Palmatine inhibits growth and invasion in prostate cancer cell: Potential role for rpS6/NFκB/FLIP. Molecular carcinogenesis 48 25043857
2019 Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy. Human molecular genetics 47 31411685
2018 Phosphorylation of Ribosomal Protein RPS6 Integrates Light Signals and Circadian Clock Signals. Frontiers in plant science 47 29403507
2019 Disruption of the MAMP-Induced MEKK1-MKK1/MKK2-MPK4 Pathway Activates the TNL Immune Receptor SMN1/RPS6. Plant & cell physiology 45 30590768
2017 mTORC1/rpS6 regulates blood-testis barrier dynamics and spermatogenetic function in the testis in vivo. American journal of physiology. Endocrinology and metabolism 41 29089336
2015 IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils. Journal of immunology (Baltimore, Md. : 1950) 38 26276876
2014 Resistance to Selumetinib (AZD6244) in colorectal cancer cell lines is mediated by p70S6K and RPS6 activation. Neoplasia (New York, N.Y.) 38 25379021
2015 The lipid peroxidation product 4-hydroxy-trans-2-nonenal causes protein synthesis in cardiac myocytes via activated mTORC1-p70S6K-RPS6 signaling. Free radical biology & medicine 36 25617592
1975 Esterase-6 (Es-6) in laboratory mice: hormone-influenced expression and linkage relationship to oligosyndactylism (Os), esterase-1 (Es-1), and esterase-2 (Es-2) in chromosome 8. Biochemical genetics 35 170908
2021 lnc-Rps4l-encoded peptide RPS4XL regulates RPS6 phosphorylation and inhibits the proliferation of PASMCs caused by hypoxia. Molecular therapy : the journal of the American Society of Gene Therapy 31 33429084
2020 p-Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1-RPS6. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 32350925
2019 mTORC1/rpS6 signaling complex modifies BTB transport function: an in vivo study using the adjudin model. American journal of physiology. Endocrinology and metabolism 29 31112404
2017 MiR-129-5p Sensitizes the Response of Her-2 Positive Breast Cancer to Trastuzumab by Reducing Rps6. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 29258115
2004 Functional interaction in establishment of ribosomal integrity between small subunit protein rpS6 and translational regulator rpL10/Grc5p. FEMS yeast research 26 15556089
2023 The p-rpS6-zone delineates wounding responses and the healing process. Developmental cell 25 37098351
2018 G protein-dependent signaling triggers a β-arrestin-scaffolded p70S6K/ rpS6 module that controls 5'TOP mRNA translation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 29084767
2016 Isolation and fine mapping of Rps6: an intermediate host resistance gene in barley to wheat stripe rust. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 25 26754419
1992 The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21. Human molecular genetics 25 1301164
2004 Secondary structure of two regions in expansion segments ES3 and ES6 with the potential of forming a tertiary interaction in eukaryotic 40S ribosomal subunits. RNA (New York, N.Y.) 23 14970386
1982 Es-6, a further polymorphic esterase in the rat. Biochemical genetics 22 7103927
2008 Adding protein to a carbohydrate supplement provided after endurance exercise enhances 4E-BP1 and RPS6 signaling in skeletal muscle. Journal of applied physiology (Bethesda, Md. : 1985) 21 18239077
2023 The RSK2-RPS6 axis promotes axonal regeneration in the peripheral and central nervous systems. PLoS biology 20 37068088
2006 Probing the secondary structure of expansion segment ES6 in 18S ribosomal RNA. Biochemistry 20 16800631
2015 Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription. Biochemical and biophysical research communications 19 26241676
2011 Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis. Experimental hematology 18 22198155
2003 A possible tertiary rRNA interaction between expansion segments ES3 and ES6 in eukaryotic 40S ribosomal subunits. RNA (New York, N.Y.) 18 12554872
2023 Quantitative proteomics and phosphoproteomics of PP2A-PPP2R5D variants reveal deregulation of RPS6 phosphorylation via converging signaling cascades. The Journal of biological chemistry 17 37572851
2019 F5-Peptide and mTORC1/rpS6 Effectively Enhance BTB Transport Function in the Testis-Lesson From the Adjudin Model. Endocrinology 17 31157869
2022 Epigallocatechin-3-gallate attenuates cyclophosphamide-induced damage in mouse ovarian tissue via suppressing inflammation, apoptosis, and expression of phosphorylated Akt, FOXO3a and rpS6. Reproductive toxicology (Elmsford, N.Y.) 16 35981663
2021 The Non-hormonal Male Contraceptive Adjudin Exerts its Effects via MAPs and Signaling Proteins mTORC1/rpS6 and FAK-Y407. Endocrinology 16 33094326
2016 Fine mapping of barley locus Rps6 conferring resistance to wheat stripe rust. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 16 26875072
2016 Inhibition of protein kinase CK2 by CX-5011 counteracts imatinib-resistance preventing rpS6 phosphorylation in chronic myeloid leukaemia cells: new combined therapeutic strategies. Oncotarget 16 26919095
2022 Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle. Amino acids 15 36474017
2019 Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex. Behavioural brain research 15 30684511
2021 RPS6 phosphorylation occurs to a greater extent in the periphery of human skeletal muscle fibers, near focal adhesions, after anabolic stimuli. American journal of physiology. Cell physiology 14 34852208
2015 Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion-Induced Kidney Growth. Journal of the American Society of Nephrology : JASN 13 26296742
2019 Regulation of blood-testis barrier dynamics by the mTORC1/rpS6 signaling complex: An in vitro study. Asian journal of andrology 12 30829292
2019 mTORC1/rpS6 and spermatogenic function in the testis-insights from the adjudin model. Reproductive toxicology (Elmsford, N.Y.) 11 31278979
2016 DsRNA-mediated targeting of ribosomal transcripts RPS6 and RPL26 induces long-lasting and significant reductions in fecundity of the vector Aedes aegypti. Journal of insect physiology 11 27180677
2020 RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics 10 32550912
2019 Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation. PLoS genetics 10 30969964
2015 Phosphorylated ribosomal S6 (p-rpS6) as a post-treatment indicator of HER2 signalling targeted drug resistance. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 10 26329528
2024 Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing. Acta pharmaceutica Sinica. B 9 39309509
2022 Midkine Promotes Metastasis and Therapeutic Resistance via mTOR/RPS6 in Uveal Melanoma. Molecular cancer research : MCR 9 35503453
2021 Members of the ribosomal protein S6 (RPS6) family act as pro-viral factor for tomato spotted wilt orthotospovirus infectivity in Nicotiana benthamiana. Molecular plant pathology 8 34913556
2018 Early changes in rpS6 phosphorylation and BH3 profiling predict response to chemotherapy in AML cells. PloS one 8 29723246
2017 Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction. Neoplasma 8 28895411
2023 Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages. Journal of inflammation research 6 38053607
2022 The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAPM/PKA/mTORC1/rpS6 Pathway. Cells 6 36078128
2007 [The TP53 and RPS6 alterations at the invasive tumor front, center and stroma of oral squamous cell carcinoma]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 5 17565818
2024 The Neurobeachin-like 2 protein (NBEAL2) controls the homeostatic level of the ribosomal protein RPS6 in mast cells. Immunology 4 38272677
2023 Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53-dependent. PLoS genetics 4 36656901
2023 mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis. Cell and tissue research 4 37328709
2013 Sexually dimorphic expression and estradiol mediated up-regulation of a sex-linked ribosomal gene, RPS6, in the zebra finch brain. Developmental neurobiology 4 23554148
2012 A genome-wide RNAi screen for polypeptides that alter rpS6 phosphorylation. Methods in molecular biology (Clifton, N.J.) 4 22125066
2024 Development of an rpS6-Based Ex Vivo Assay for the Analysis of Neuronal Activity in Mouse and Human Olfactory Systems. International journal of molecular sciences 3 39684883
2022 RPS6 transcriptional modulation in neural tissues of Nauphoeta cinerea during streptozotocin-associated sugar metabolism impairment. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 3 35931314
2011 [Molecular analysis of TP53, D9S1747, D9S162 and RPS6 in oral squamous cell carcinoma]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 3 21418946
1995 The mammalian RPS6 gene, homolog of the Drosophila air8 tumor suppressor gene: is it an oncosuppressor gene? Somatic cell and molecular genetics 3 8600571
2025 HN1 Functions in Protein Synthesis Regulation via mTOR-RPS6 Axis and Maintains Nucleolar Integrity. Cell proliferation 2 39805577
2025 Multi-omics profiling of metastatic colorectal cancer reveals the transcriptional network of focal adhesion and immune suppression and the role of p-RPS6. Cancer cell international 2 40770803
2024 Expression of PD-L1 and p-RPS6 in epithelial dysplasia and squamous cell carcinoma of the oral cavity. Frontiers in oral health 2 38370876
2023 Quantitative proteomics and phosphoproteomics of PPP2R5D variants reveal deregulation of RPS6 phosphorylation through converging signaling cascades. bioRxiv : the preprint server for biology 2 37034727
2007 Histone H1-like, lysine-rich low complexity amino acid extensions in mosquito ribosomal proteins RpL23a and RpS6 have evolved independently. Archives of insect biochemistry and physiology 2 17212354
2003 Construction and characterization of a soybean yeast artificial chromosome library and identification of clones for the Rps6 region. Functional & integrative genomics 2 14520523
2025 Translation of nervous necrosis virus involves eIF4E but not RPS6 phosphorylation and viral particle assembly in remodeled microtubule-organizing center. Virology journal 1 41146207
2023 Quantitative proteomics profiling reveals the inhibition of trastuzumab antitumor efficacy by phosphorylated RPS6 in gastric carcinoma. Cancer chemotherapy and pharmacology 1 37507485
2023 Complete genome sequence of Cellulomonas sp., strain ES6, a chromate-reducing bacterium isolated from chromium-contaminated subsurface sediment. Microbiology resource announcements 1 37681972
2014 [Construction of sh-rpS6 lentivirus vectors and its effect on proliferation in lung adenocarcinoma A549 cell lines]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 1 24749361
2026 Protein levels of p-mTOR and p-RPS6 in cumulus cells serve as non-invasive biomarkers for embryo quality and pregnancy outcome in IVF. Journal of assisted reproduction and genetics 0 41609915
2026 Targeted capture and cloning of Rps6 reveal redundancy in soybean resistance genes. BMC plant biology 0 41703460
2025 Correction: Retraction: Tanshinone IIA Inhibits HIF-1α and VEGF Expression in Breast Cancer Cells via mTOR/p70S6K/RPS6/4E-BP1 Signaling Pathway. PloS one 0 40354300
2025 Possible involvement of p60-S6K1 in accelerating RPS6 phosphorylation for rapid recovery from skeletal muscle disuse atrophy. Laboratory animal research 0 40931334
2025 Histamine-induced RPS6 phosphorylation in dendritic cells is associated with the severity of peanut allergic reactions. JCI insight 0 40932794
2025 Vesicular Rps6 Released by Astrocytes in an Experimental Model of AD Regulates Local Translation and Enhances Synaptic Integrity in Neurones. Journal of extracellular vesicles 0 41416952
2023 [Stable Expression of Coagulation Factors by RPS6 Promoter]. Zhongguo shi yan xue ye xue za zhi 0 37096524

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