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Showing RACK1 — GNB2L1 is a alias.

RACK1

Small ribosomal subunit protein RACK1 · UniProt P63244

Length
317 aa
Mass
35.1 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 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

RACK1 is a WD40 β-propeller scaffold that constitutively occupies the head of the 40S ribosomal subunit near the mRNA exit channel, where it recruits activated PKC to couple signaling to translational control (PMID:15577927, PMID:31023766). On the ribosome it pairs with PKCβII to drive eIF4E phosphorylation and preferential cap-dependent translation of growth and survival factors, a function exploited in hepatocellular carcinoma and tuned by O-GlcNAcylation at Ser122, which strengthens ribosome binding and PKCβII engagement (PMID:22653060, PMID:29454068). RACK1 is also required for IRES-dependent translation of viral mRNAs and serves as a ribosomal platform for mRNA-specific factors, recruiting miRISC for miRNA-mediated repression, scaffolding the β-actin mRNA/ZBP1 complex, and partnering with Vigilin/SERBP1 to support flaviviral replication (PMID:25416947, PMID:21525958, PMID:22523568, PMID:35266803). Beyond the ribosome, RACK1 functions as a multivalent signaling adaptor: it links PKC to integrins, scaffolds PKC-dependent JNK activation through Ser129 phosphorylation, and binds Src family kinases via phosphorylated Tyr228/Tyr246 to control focal adhesion dynamics, migration, osteoclast cytoskeletal integrity, and E-cadherin–based cell adhesion (PMID:9442085, PMID:16061178, PMID:12400005, PMID:12589061, PMID:31358728, PMID:21685945). It additionally acts as a conformational and degradative regulator of innate immune and stress pathways — promoting the active conformation of NLRP3 to license inflammasome assembly, attenuating RIG-I/MAVS antiviral signaling, and competing with HSP90 to drive HIF-1α degradation via the Elongin-C/B ligase (PMID:33207200, PMID:30527812, PMID:17361105). RACK1 scaffolds developmental and stress signaling including PKCα-mediated BMAL1 phosphorylation in the circadian clock, Hedgehog pathway control of Ci and Smo, and suppression of TGF-β/Smad3/p21 signaling that prevents neural stem cell senescence during cortical development (PMID:20093473, PMID:32467643, PMID:34469723). RACK1 abundance and localization are themselves controlled by an extensive set of post-translational modifications, including PARP14-mediated MARylation that drives stress granule association and translational repression, and polyubiquitination by multiple ligases (SMURF2, TRIM26, SPOP) and the E3-independent conjugating enzyme UBE2T (PMID:39760726, PMID:37828084, PMID:37591850, PMID:37442135, PMID:33323973).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Established RACK1 as a PKC-dependent adaptor linking signaling kinases to membrane receptors, defining its core scaffold function before any ribosomal role was known.

    Evidence Yeast two-hybrid and reciprocal Co-IP with integrin β cytoplasmic tails in 293T/JY cells

    PMID:9442085

    Open questions at the time
    • Did not resolve whether integrin binding occurs on or off the ribosome
    • Structural basis of the WD5–7 interaction surface not determined
  2. 2002 High

    Defined RACK1 as both a Src substrate and an inhibitory scaffold for tyrosine kinases, showing it can suppress rather than only relay kinase activity.

    Evidence In vitro kinase assays with Src mutants and Tyr228/246 mutagenesis; Co-IP and hippocampal electrophysiology with peptide disruption of RACK1–NR2B–Fyn

    PMID:11943848 PMID:12400005

    Open questions at the time
    • Mechanism by which a single scaffold both binds and inhibits Src/Fyn not structurally resolved
    • Tissue-specific selection between activating and inhibitory outputs unclear
  3. 2004 High

    Placed RACK1 physically on the 40S ribosome head near the mRNA exit channel, transforming it from a cytoplasmic adaptor into a structural link between signaling and translation.

    Evidence Cryo-EM localization and biochemical reconstitution

    PMID:15577927

    Open questions at the time
    • How ribosomal versus extra-ribosomal pools are partitioned not defined
    • Direct evidence of eIF6 phosphorylation in cells limited
  4. 2005 High

    Showed RACK1 acts as a priming scaffold for the JNK cascade, demonstrating it organizes MAPK signaling and not only PKC localization.

    Evidence Phospho-specific antibodies, in vitro kinase assays, Ser129 mutagenesis, and siRNA knockdown across multiple stimuli

    PMID:16061178

    Open questions at the time
    • Whether JNK priming occurs on the ribosome not addressed
    • Stoichiometry of the PKC–JNK–RACK1 assembly unknown
  5. 2006 Medium

    Connected RACK1's Src inhibition to cell-cycle checkpoint control and growth suppression, expanding its role into proliferation regulation.

    Evidence Overexpression/depletion, cell-permeable peptide disruption, and cell-cycle/kinase assays in colon cells

    PMID:17072338

    Open questions at the time
    • Single lab; in vivo cell-cycle relevance not established
    • Link between Sam68 phosphorylation and CDK1-cyclin B regulation indirect
  6. 2007 Medium

    Revealed an O2/VHL-independent route to HIF-1α turnover in which RACK1 acts as a degradation adaptor competing with a chaperone.

    Evidence Competitive binding, Co-IP, and ubiquitination/stability assays with the Elongin-C/B complex

    PMID:17361105

    Open questions at the time
    • Physiological conditions favoring RACK1 over HSP90 binding undefined
    • In vivo contribution to hypoxic signaling not tested
  7. 2010 Medium

    Extended RACK1 to nuclear scaffolding of clock and chromatin machinery, showing it times PKCα-mediated transcriptional repression and gene-specific transcription.

    Evidence Co-IP from mouse liver, in vitro kinase assays, siRNA period-length measurement; ChIP at BDNF promoter IV with MeCP2 displacement readout

    PMID:20093473 PMID:20410295

    Open questions at the time
    • How RACK1 is targeted to specific nuclear loci unresolved
    • Relationship between nuclear and ribosomal pools not defined
  8. 2012 High

    Established that ribosomal RACK1 couples PKCβII to eIF4E phosphorylation for selective mRNA translation and recruits mRNA-specific factors, mechanistically tying its scaffold role to translational selectivity.

    Evidence Ribosome-binding mutants, eIF4E phospho-assays, Co-IP with ZBP1 and miRISC, polysome fractionation, and xenograft validation

    PMID:21525958 PMID:22523568 PMID:22653060

    Open questions at the time
    • Rules governing which mRNAs are selected not fully defined
    • Direct contacts between RACK1 and individual mRNP factors not structurally mapped
  9. 2014 High

    Demonstrated RACK1 is specifically required for IRES-dependent viral translation without affecting bulk translation, distinguishing a dedicated translational function.

    Evidence RNAi in Drosophila and human cells with CrPV/HCV IRES reporters and HCV infection assays

    PMID:25416947

    Open questions at the time
    • Molecular basis for IRES vs. cap-dependent discrimination not resolved
    • Whether host IRES mRNAs share this dependence unknown
  10. 2018 High

    Identified O-GlcNAcylation at Ser122 as a regulatory switch enhancing ribosome binding and oncogenic translation, providing a genetic in vivo link to tumorigenesis.

    Evidence MS site mapping, Ser122 knock-in mice, Co-IP, eIF4E phospho-assay, and DEN-induced HCC model

    PMID:29454068

    Open questions at the time
    • Upstream signals controlling RACK1 O-GlcNAcylation unknown
    • Interplay with other RACK1 PTMs not examined
  11. 2020 High

    Defined a ribosome-independent role for RACK1 as a conformational chaperone for NLRP3 inflammasome activation, including a pathogen-driven deubiquitination axis.

    Evidence Co-IP with NLRP3/NEK7, ribosomal-binding mutant, stimulus-specific caspase-1/IL-1β readouts; EST12 crystal structure and UCHL5-mediated NLRP3 deubiquitination

    PMID:33097533 PMID:33207200

    Open questions at the time
    • Structural basis of RACK1 stabilizing active NLRP3 conformation not solved
    • How RACK1 partitions between inflammasome and ribosome pools unresolved
  12. 2021 High

    Established a developmental in vivo requirement for RACK1 in suppressing TGF-β/Smad3/p21-driven neural stem cell senescence, with genetic rescue confirming the pathway.

    Evidence Conditional knockout mice, p21-deletion rescue, Rack1–Smad3 Co-IP, and cortical development phenotyping

    PMID:34469723

    Open questions at the time
    • Direct mechanism of Smad3 inhibition by RACK1 not structurally defined
    • Whether ribosomal RACK1 contributes to this phenotype untested
  13. 2023 Medium

    Mapped a network of E3 ligases and conjugating enzymes that control RACK1 stability through distinct ubiquitin linkages and acetylation crosstalk, explaining context-dependent RACK1 abundance.

    Evidence Co-IP, K-linkage-specific ubiquitination assays, site mutagenesis, and rescue experiments for SMURF2, TRIM26, SPOP, and UBE2T across multiple cancer/fibrosis models

    PMID:33323973 PMID:37442135 PMID:37591850 PMID:37828084

    Open questions at the time
    • Whether these ligases act on distinct RACK1 pools is unknown
    • Hierarchy and combinatorial logic among the modifications undefined
  14. 2025 High

    Showed PARP14-mediated MARylation redirects RACK1 into stress granules to repress translation of specific mRNAs, defining a reversible PTM that toggles RACK1 between active translation and sequestration.

    Evidence ADP-ribosylation assays, MARylation-site mutagenesis, stress granule imaging, polysome profiling, and in vivo tumor growth in ovarian cancer cells

    PMID:39760726

    Open questions at the time
    • MARylated residues and their structural effect on the propeller not fully mapped
    • Interplay with O-GlcNAcylation and ubiquitination during stress not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cell partitions a single RACK1 scaffold among its ribosomal, nuclear, inflammasome, focal-adhesion, and stress-granule functions, and how the various PTMs are integrated to dictate this partitioning, remains unresolved.
  • No unified model for spatial allocation of RACK1 pools
  • Stoichiometry and competition among the many partners not measured
  • Combinatorial PTM logic governing localization and stability undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 2
Localization
GO:0005634 nucleus 3 GO:0005840 ribosome 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-8953854 Metabolism of RNA 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-9612973 Autophagy 2 R-HSA-9909396 Circadian clock 1
Partners
ATG5BMAL1FYNNEK7NLRP3PKCSMAD3SRC
Complex memberships
40S ribosomal subunitNLRP3 inflammasomemiRISCstress granule

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 RACK1 interacts with integrin β subunit cytoplasmic domains via WD repeats 5–7; full-length RACK1 association with integrins in vivo requires phorbol ester treatment, suggesting RACK1 links PKC to integrins to regulate integrin function. Yeast two-hybrid, co-immunoprecipitation in 293T and JY cells, deletion mapping The Journal of biological chemistry High 9442085
2002 RACK1 binds both the NR2B subunit of the NMDA receptor and Fyn tyrosine kinase, acting as an inhibitory scaffold; RACK1 inhibits Fyn-mediated phosphorylation of NR2B and decreases NMDA receptor-mediated currents in hippocampal slices. Disrupting RACK1–NR2B–Fyn interactions with peptides induces NR2B phosphorylation and potentiates NMDA currents. Co-immunoprecipitation, electrophysiology in CA1 hippocampal slices, cell-permeable peptide disruption assays Proceedings of the National Academy of Sciences of the United States of America High 11943848
2002 RACK1 is a substrate of Src tyrosine kinase; Src phosphorylates RACK1 on Tyr228 and/or Tyr246 (located in the sixth WD repeat), and this phosphorylation is required for RACK1 binding to Src's SH2 domain following PKC activation. In vitro kinase assay with various tyrosine kinases, in vivo kinase-active/inactive Src mutants, site-directed mutagenesis of RACK1 tyrosines Oncogene High 12400005
2003 RACK1 regulates focal adhesion organization, cell protrusion, and chemotactic migration via its Src-binding site; a point mutant (Y246F) that does not bind Src abolishes RACK1-dependent regulation of protrusion and migration. RACK1 localizes to nascent focal complexes in protrusive regions. GFP-tagged RACK1 live-cell imaging, point-mutant expression, chemotaxis assay, focal adhesion morphology screen in CHO-K1 cells Molecular biology of the cell High 12589061
2004 RACK1 is a constituent of the eukaryotic 40S ribosomal subunit, localized by cryo-electron microscopy to the head region near the mRNA exit channel, where it recruits activated PKC to stimulate translation through phosphorylation of eIF6. Cryo-electron microscopy structural localization, biochemical reconstitution EMBO reports High 15577927
2005 RACK1 serves as an adaptor for PKC-mediated JNK activation; PKC phosphorylates JNK on Ser129 in a RACK1-dependent manner, and this phosphorylation augments subsequent MKK4/MKK7-mediated JNK activation. siRNA-mediated RACK1 depletion attenuates JNK activation by TPA, TNFα, UV, and PKC. Phospho-specific antibodies, in vitro kinase assays, siRNA knockdown, site-directed mutagenesis (Ser129) Molecular cell High 16061178
2006 RACK1 inhibits Src activity at G1 and mitotic cell cycle checkpoints to suppress colon cell growth; it suppresses Src-mediated Sam68 phosphorylation and maintains CDK1-cyclin B in an active state. Cell-permeable peptides disrupting RACK1–Src interaction abolish these effects. RACK1 overexpression and depletion, cell-permeable peptide disruption, cell cycle analysis, kinase activity assays Oncogene Medium 17072338
2007 RACK1 promotes O2/PHD/VHL-independent proteasomal degradation of HIF-1α by competing with HSP90 for binding to the HIF-1α PAS-A domain, then recruiting Elongin-C/B E3 ubiquitin ligase complex to HIF-1α to drive its ubiquitination and degradation. Co-immunoprecipitation, ubiquitination assays, competitive binding assays, overexpression/knockdown with HIF-1α stability readout Cell cycle (Georgetown, Tex.) Medium 17361105
2010 RACK1 and PKCα are recruited in a circadian manner into a nuclear BMAL1 complex during the negative feedback phase of the mammalian clock; RACK1 stimulates PKCα-mediated phosphorylation of BMAL1 in vitro, suppressing CLOCK-BMAL1 transcriptional activity. Depletion of RACK1 or PKCα shortens the circadian period. Co-immunoprecipitation from mouse liver, in vitro kinase assay, siRNA depletion in fibroblasts with period-length measurement, overexpression transcriptional reporter assay Science (New York, N.Y.) High 20093473
2010 Nuclear RACK1 associates with histone H3 and H4 at the BDNF gene promoter IV region following cAMP pathway activation, displaces the transcriptional repressor MeCP2, and promotes histone H4 acetylation, leading to exon IV-specific BDNF transcription. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, knockdown, RT-PCR for exon-specific BDNF expression The Journal of biological chemistry Medium 20410295
2011 RACK1 interacts with Flt1 (VEGFR-1) in vitro and mediates VEGF/Flt1-driven cell migration through activation of the PI3K/Akt and Rac1 pathways; RACK1 siRNA suppresses VEGF-driven migration without affecting proliferation. In vitro binding assay, RNAi knockdown, PI3K/Akt pathway activation assays, migration assay The Journal of biological chemistry Medium 21212275
2011 RACK1 promotes epithelial cell–cell adhesion by inhibiting Src-mediated E-cadherin phosphorylation, preventing Hakai-mediated E-cadherin ubiquitination and endocytosis, thereby stabilizing E-cadherin and catenins at cell–cell contacts and reducing invasive potential. RACK1 depletion/overexpression, Src activity assays, E-cadherin ubiquitination/endocytosis assays, calcium-switch assay Oncogene Medium 21685945
2011 RACK1 interacts with components of the miRNA-induced silencing complex (miRISC) in C. elegans and mammals; RACK1 contributes to recruitment of miRISC to translating ribosomes and is required for miRNA-mediated gene repression (post-initiation mode). Co-immunoprecipitation of RACK1 with miRISC components in vivo, RACK1 overexpression/knockdown with miRNA reporter readouts, polysome fractionation EMBO reports High 21525958
2012 Ribosomal RACK1 couples with PKCβII to promote phosphorylation of eIF4E, leading to preferential cap-dependent translation of growth and survival factors and contributing to HCC chemoresistance; ribosome localization of RACK1 is required for this effect. Co-immunoprecipitation, eIF4E phosphorylation assays, ribosome-binding mutants, PKCβII inhibition, siRNA knockdown, in vivo xenograft The Journal of clinical investigation High 22653060
2012 RACK1 acts as a ribosomal scaffold protein for the β-actin mRNA/ZBP1 complex; RACK1 Y246 (Src phosphorylation/binding site) is required for binding to the β-actin mRNA/ZBP1 complex, contributing to release of β-actin mRNA from ZBP1 and its translation. Co-immunoprecipitation of RACK1 with ZBP1 on ribosomes, site-directed mutagenesis (Y246F), mRNA translation assay in neurons PloS one Medium 22523568
2014 RACK1 is an essential determinant for IRES-mediated viral translation (cricket paralysis virus, hepatitis C virus); RACK1 knockdown does not affect general translation or cell viability but specifically impairs IRES-dependent translation and viral infection. RNAi in Drosophila and human cells, viral IRES reporter translation assays, HCV infection assays Cell High 25416947
2014 TRIM45 directly interacts with RACK1 and downregulates PKC/MAPK signaling; TRIM45 expression is induced by MAPK pathway activation and attenuates signaling in a negative feedback manner. Co-immunoprecipitation, MAPK pathway reporter assays, TRIM45 overexpression/knockdown Oncogene Medium 24681954
2014 DJ-1 interacts with RACK1, increases RACK1 dimerization and protein stability, and the DJ-1–RACK1 complex protects cortical neurons from H2O2-induced apoptosis; disruption of this interaction by H2O2 or MPP+ sensitizes neurons to oxidative damage. Co-immunoprecipitation, crosslinking/dimerization assays, RACK1 knockdown with neuronal apoptosis readout The Biochemical journal Medium 24947010
2016 RACK1 interacts with ATG5 and is a novel regulator of autophagy; classical autophagy inducers (starvation, mTOR blockade) stimulate RACK1–ATG5 interaction, and knockdown of RACK1 or prevention of its ATG5 binding by mutagenesis blocks autophagy activation. Co-immunoprecipitation, mutagenesis, multiple autophagy inducers, knockdown with LC3-II/autophagosome formation readout The Journal of biological chemistry Medium 27325703
2017 Yeast RACK1 ortholog Asc1p is phosphorylated at T143 and Y250; T143 phosphorylation is required for ribosome-binding stability (mutation to dephosphorylation-mimicking Ala destabilizes Asc1DEp), and Asc1p/RACK1 influences phosphorylation of ~90 proteins at 120 sites involved in translation, cytoskeleton, and signaling. Phospho-site mutagenesis (T143A, Y250F), ribosome-binding assays, quantitative phosphoproteomics Molecular and cellular biology Medium 27821475
2018 O-GlcNAcylation of RACK1 at Ser122 enhances its protein stability, ribosome binding, and interaction with PKCβII, leading to increased eIF4E phosphorylation and translation of oncogenes; genetic ablation of Ser122 O-GlcNAcylation suppresses HCC tumorigenesis in vivo. Mass spectrometry mapping of O-GlcNAc site, Ser122 knock-in mice, co-immunoprecipitation, eIF4E phosphorylation assay, in vivo DEN-induced HCC model Journal of hepatology High 29454068
2018 RACK1 interacts with VISA (MAVS) and attenuates RIG-I/VISA-mediated antiviral signaling by disrupting VISA-TRAF2, VISA-TRAF3, and VISA-TRAF6 complexes; RACK1 promotes K48-linked ubiquitination of VISA and reduces its K63-linked ubiquitination, decreasing VISA-mediated IFN-β production. Co-immunoprecipitation, overexpression/siRNA knockdown, IFN-β promoter reporter assays, IRF3 dimerization assay, ubiquitination assays Biochemical and biophysical research communications Medium 30527812
2019 RACK1 interaction with c-Src via RACK1 Tyr228/Tyr246 is essential for osteoclast function; a RACK1 Y228F/Y246F double mutant retains osteoclast differentiation but abolishes cytoskeletal integrity, bone resorption, and c-Src phosphorylation. Lys152 in the Src SH2 domain mediates RACK1 binding. Site-directed mutagenesis of RACK1 and c-Src, co-immunoprecipitation, osteoclast bone resorption assay, cytoskeleton imaging Experimental & molecular medicine Medium 31358728
2019 RACK1 mediates HCV-induced rewiring of subcellular membranes and autophagy induction; RACK1 binds HCV NS5A protein and promotes NS5A interaction with ATG14L in a RACK1-dependent manner, facilitating formation of the ATG14L-Beclin1-Vps34-Vps15 autophagosome-initiation complex and HCV double-membrane vesicle replication organelles. Yeast two-hybrid screening, co-immunoprecipitation, RACK1 depletion with HCV RNA replication readout, electron microscopy of DMVs PLoS pathogens Medium 31525236
2020 Mycobacterium tuberculosis EST12 binds RACK1 in macrophages; the EST12–RACK1 complex recruits deubiquitinase UCHL5 to promote K48-linked deubiquitination of NLRP3, leading to NLRP3 inflammasome activation and pyroptosis. Crystal structure of EST12 reveals Y80 as the critical RACK1-binding residue. Co-immunoprecipitation, crystal structure of EST12, mutagenesis (Y80), ubiquitination assays, pyroptosis/caspase-1 activation assays Science advances High 33097533
2020 RACK1 is a component of NLRP3 inflammasome complexes; RACK1 interacts with NLRP3 and NEK7 (but not ASC), promotes the active conformation of NLRP3 upon activating stimuli, and facilitates subsequent inflammasome assembly. RACK1 suppression abolishes caspase-1 activation and IL-1β release specifically in response to NLRP3- but not NLRC4- or AIM2-activating stimuli. This function is independent of ribosomal binding. Co-immunoprecipitation, siRNA knockdown with stimulus-specific caspase-1/IL-1β readout, conformational assay, ribosomal binding mutant Cell reports High 33207200
2020 UBE2T promotes ubiquitination and degradation of RACK1 at Lys172, Lys225, and Lys257 independently of an E3 ligase, leading to Wnt/β-catenin pathway hyperactivation and gastric cancer progression; pharmacological UBE2T inhibition blocks RACK1 degradation. Co-immunoprecipitation, ubiquitination site mapping by mutagenesis, in vivo tumor models, UBE2T inhibitor Oncogene Medium 33323973
2020 Rack1 is required for Hedgehog signaling through dual mechanisms: in the absence of Hh, Rack1 promotes formation of a Ci–Rack1–Cos2 complex leading to Slimb-mediated Ci proteolysis; in the presence of Hh, Rack1 dissociates from this complex, forms a trimeric complex with Smo and Usp8 leading to Smo deubiquitination and cell surface accumulation. This regulation is conserved from Drosophila to mammals. Co-immunoprecipitation, genetic epistasis in Drosophila, cell surface accumulation assays, deubiquitination assays, mammalian cell validation Cell death and differentiation High 32467643
2021 Rack1 directly interacts with Smad3 to suppress TGF-β/Smad signaling and downstream p21-mediated senescence in neural stem cells; conditional deletion of Rack1 in cortical progenitors causes microcephaly via p21-dependent NSC senescence, and removal of p21 rescues the Rack1-KO phenotype in vivo. Conditional knockout mice, genetic rescue (p21 deletion), co-immunoprecipitation of Rack1–Smad3, p21 pathway analysis, in vivo cortical development phenotype Cell reports High 34469723
2022 RACK1 associates with RNA-binding proteins Vigilin and SERBP1 at the 40S ribosomal subunit to facilitate dengue virus (DENV) replication; Vigilin and SERBP1 interact with the DENV genome, and mutants lacking RACK1-binding but retaining viral RNA-binding cannot mediate DENV infection. RACK1 interactome by mass spectrometry, RNAi screen, genetic ablation of Vigilin/SERBP1, RACK1-binding mutants of Vigilin/SERBP1 with viral replication readout Journal of virology Medium 35266803
2023 SMURF2 is an E3 ubiquitin ligase for RACK1, adding K6, K33, and K48 polyubiquitin chains to RACK1; PCAF-mediated acetylation of RACK1 at K130 inhibits SMURF2-mediated ubiquitination. Loss of SMURF2 increases RACK1 stability and promotes ovarian cancer progression. Co-immunoprecipitation, ubiquitination assays with K-linkage specific antibodies, acetylation assays, mutagenesis of K130 Cell death and differentiation Medium 37828084
2023 TRIM26 interacts with RACK1 and promotes its proteasomal degradation, thereby inactivating MEK/ERK signaling and suppressing osteosarcoma progression; overexpression of RACK1 rescues the inhibitory effect of TRIM26 overexpression on p-MEK/p-ERK. Co-immunoprecipitation, gain/loss-of-function with MEK/ERK readout, rescue experiments with RACK1 overexpression Cell death & disease Medium 37591850
2023 FMRP maintains RACK1 protein levels in human prenatal neurons by interacting with CNOT1 to regulate RACK1 as a species-specific target; genetic reduction of RACK1 reproduces FXS-like mitochondrial dysfunction and hyperexcitability. Multiomics (FMRP-bound mRNA/protein interactome), RACK1 knockdown in human fetal cortical neurons with mitochondrial function and electrophysiology readouts Neuron Medium 37820724
2025 RACK1 is MARylated by PARP14 in ovarian cancer cells; MARylation promotes RACK1 association with stress granules (colocalizing with G3BP1, eIF3η, 40S proteins) and reduces translation of a subset of mRNAs including AKT. TARG1 deMARylates RACK1 to dissolve stress granules and restore translation. PARP14 inhibition or mutation of MARylation sites on RACK1 blocks stress granule formation and reduces tumor growth. ADP-ribosylation assays, PARP14 inhibitor, RACK1 MARylation-site mutagenesis, stress granule imaging with colocalization, polysome profiling, in vivo tumor growth assay The Journal of cell biology High 39760726
2009 RACK1 physically interacts with WRN helicase/exonuclease via the WRN RQC domain; purified RACK1 selectively inhibits WRN exonuclease activity in vitro without affecting helicase activity. Depletion of WRN causes nuclear RACK1 to translocate to the membrane fraction where it activates PKCδ and PKCβII. Tandem affinity purification, in vitro exonuclease/helicase assays, domain-mapping, cellular fractionation with PKC activation readout Oncogene Medium 19966859
2013 MCM7 interacts with RACK1 in vivo and in vitro via MCM7 amino acids 221–248; RACK1 scaffolds Akt in proximity to MCM7, promoting Akt-dependent MCM7 phosphorylation, which increases MCM7 chromatin association and DNA replication. MCM7 mutants that do not bind RACK1 lack DNA replication licensing activity. Co-immunoprecipitation in vivo and in vitro, domain mapping, MCM7 binding-deficient mutant, chromatin fractionation, DNA synthesis assay The American journal of pathology Medium 23313748
2001 RACK1 interacts with the PH domain of p120GAP (RasGAP) in vivo and in vitro; deletion of the PH or C2/CaLB domain of p120GAP abolishes the interaction, and serine/threonine phosphorylation regulates this association. Co-immunoprecipitation, GST pulldown with recombinant RACK1, domain-deletion mutants of p120GAP Biochemical and biophysical research communications Medium 11350068
2001 HIV-1 Nef binds the C-terminal moiety of RACK1 in yeast two-hybrid and cell-free pulldown assays; Nef and RACK1 partially colocalize on the trans-Golgi network and plasma membrane; RACK1 doubles Nef phosphorylation by PKC in vitro, suggesting RACK1 acts as a Nef–PKC docking adaptor. Yeast two-hybrid, cell-free pulldown, co-purification, in vitro PKC phosphorylation assay, colocalization by microscopy Virology Medium 11312657
2006 RACK1 binds the BKCa (large conductance Ca2+-activated K+) channel intracellular C-terminal tail; interaction confirmed by GST pulldown and co-immunoprecipitation; co-localization observed in vascular smooth muscle cells; RACK1 affects BKCa channel biophysical properties, suggesting RACK1 forms part of a BKCa regulatory complex. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, immunocytochemistry, electrophysiology American journal of physiology. Cell physiology Medium 17166942
2023 SPOP recognizes Ser/Thr-rich motifs on RACK1 and promotes its ubiquitination and proteasomal degradation via the CUL3/RING E3 ligase complex, leading to Smad3-mediated cardiac fibroblast activation and exacerbated cardiac fibrosis after myocardial infarction. Co-immunoprecipitation, ubiquitination assays, lentiviral knockdown/overexpression, RACK1 forced expression rescue in SPOP-overexpressing CFs, in vivo MI mouse model Cell chemical biology Medium 37442135
2024 c-Abl kinase maintains RACK1 protein stability at focal adhesions, where RACK1 serves as a scaffold for c-Abl and FAK, driving fibroblast activation and myofibroblast differentiation during renal fibrosis; c-Abl deletion reduces RACK1 expression and diminishes fibrosis. Fibroblast-specific c-Abl conditional KO mice, co-immunoprecipitation, western blot, fibrosis readouts in vivo Cell communication and signaling : CCS Medium 38689280
2022 RACK1 is required for vaccinia virus postreplicative mRNA translation (via 5′ polyA leaders) independently of its role in ribosome-based stress signaling; RACK1 KO blunts JNK activation during infection only as an indirect consequence of reduced viral protein accumulation, not through direct RSR-mediated signaling. RACK1 knockout cells, viral protein synthesis assays, JNK inhibitors vs. RACK1 KO comparison, RSR activation assays Journal of virology Medium 36098514
2019 RACK1 stably reassociates with the human 40S ribosomal subunit, displays limited conformational dynamics, and remains bound for hours in vitro; fluorescently labeled RACK1 can be used as a stable ribosome tag for single-molecule translation studies. Bulk and single-molecule FRET/fluorescence biochemical assays, engineered fluorescent human RACK1–ribosome complexes RNA (New York, N.Y.) Medium 31023766

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 RACK1, A multifaceted scaffolding protein: Structure and function. Cell communication and signaling : CCS 372 21978545
1998 Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit. The Journal of biological chemistry 301 9442085
2004 Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome. EMBO reports 236 15577927
2005 RACK1 mediates activation of JNK by protein kinase C [corrected]. Molecular cell 158 16061178
2002 NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proceedings of the National Academy of Sciences of the United States of America 156 11943848
2014 RACK1, a versatile hub in cancer. Oncogene 155 24882575
2017 Roles for RACK1 in cancer cell migration and invasion. Cellular signalling 151 28336233
2014 RACK1 controls IRES-mediated translation of viruses. Cell 149 25416947
2007 RACK1 vs. HSP90: competition for HIF-1 alpha degradation vs. stabilization. Cell cycle (Georgetown, Tex.) 140 17361105
2003 RACK1 regulates integrin-mediated adhesion, protrusion, and chemotactic cell migration via its Src-binding site. Molecular biology of the cell 126 12589061
2012 Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma. The Journal of clinical investigation 124 22653060
2010 Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock. Science (New York, N.Y.) 109 20093473
2006 RACK1 has the nerve to act: structure meets function in the nervous system. Progress in neurobiology 105 16457939
2020 Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1β immune pathway. Science advances 100 33097533
2018 O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis. Journal of hepatology 96 29454068
2002 RACK1: a novel substrate for the Src protein-tyrosine kinase. Oncogene 95 12400005
2011 RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. The Journal of biological chemistry 91 21212275
2020 A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. Oncogene 87 33323973
2012 RACK1 promotes non-small-cell lung cancer tumorigenicity through activating sonic hedgehog signaling pathway. The Journal of biological chemistry 79 22262830
1997 The role of anchoring protein RACK1 in PKC activation in the ageing rat brain. Trends in neurosciences 79 9292970
2019 RACK1 promotes the invasive activities and lymph node metastasis of cervical cancer via galectin-1. Cancer letters 71 31705928
2006 RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints. Oncogene 69 17072338
2011 The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans. EMBO reports 67 21525958
2020 Endocrine-Disrupting Chemicals' (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1. International journal of molecular sciences 66 33287384
2013 RACK1 Function in Cell Motility and Protein Synthesis. Genes & cancer 66 24349634
2020 RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly. Cell reports 64 33207200
2004 Interaction of Gbetagamma with RACK1 and other WD40 repeat proteins. Journal of molecular and cellular cardiology 61 15276010
2009 RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Breast cancer research and treatment 58 19946739
2021 PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex. Cell death & disease 56 33723221
2018 RACK1 promotes tumorigenicity of colon cancer by inducing cell autophagy. Cell death & disease 54 30451832
2010 Epigenetic regulation of BDNF expression via the scaffolding protein RACK1. The Journal of biological chemistry 54 20410295
2017 Structural analysis of ribosomal RACK1 and its role in translational control. Cellular signalling 51 28161490
2019 RACK1 on and off the ribosome. RNA (New York, N.Y.) 47 31023766
2012 RACK1 is a ribosome scaffold protein for β-actin mRNA/ZBP1 complex. PloS one 45 22523568
2021 PHB2 promotes tumorigenesis via RACK1 in non-small cell lung cancer. Theranostics 40 33537079
2016 RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy. The Journal of biological chemistry 40 27325703
2011 Rack1 promotes epithelial cell-cell adhesion by regulating E-cadherin endocytosis. Oncogene 39 21685945
2019 RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection. PLoS pathogens 37 31525236
2014 The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway. Oncogene 36 24681954
2012 RACK1 research - ships passing in the night? FEBS letters 36 22580388
2008 Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation. Molecular cancer 36 18442364
2001 RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP. Biochemical and biophysical research communications 36 11350068
2015 RACK1, scaffolding a heterotrimeric G protein and a MAPK cascade. Trends in plant science 35 25986967
2001 Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor. Virology 35 11312657
2017 RACK1 regulates neural development. Neural regeneration research 34 28852378
1999 Structure and genomic organization of porcine RACK1 gene. Biochimica et biophysica acta 34 10673032
2021 Effects of Bisphenols on RACK1 Expression and Their Immunological Implications in THP-1 Cells. Frontiers in pharmacology 33 34621174
2017 Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling. Molecular and cellular biology 33 27821475
2013 RACK1 to the future--a historical perspective. Cell communication and signaling : CCS 33 23915285
2023 Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression. Cell death and differentiation 32 37828084
2019 Cortisol-induced SRSF3 expression promotes GR splicing, RACK1 expression and breast cancer cells migration. Pharmacological research 32 30862604
2020 OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression. Oncogenesis 31 33311444
2015 RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway. International journal of molecular medicine 31 26718491
1997 Ischemia-induced receptor for activated C kinase (RACK1) expression in rat kidneys. The American journal of physiology 31 9124391
2017 RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex. Oncotarget 30 28465488
2014 DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis. The Biochemical journal 30 24947010
2023 Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation. Acta pharmacologica Sinica 29 37225849
2023 Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. Neuron 29 37820724
2022 RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication. Journal of virology 29 35266803
2008 Functional mapping of the promoter region of the GNB2L1 human gene coding for RACK1 scaffold protein. Gene 29 19000751
2020 Ribosomal protein RACK1 enhances translation of poliovirus and other viral IRESs. Virology 28 32308198
2013 AChE and RACK1 promote the anti-inflammatory properties of fluoxetine. Journal of molecular neuroscience : MN 27 24258317
2021 Rack1 is essential for corticogenesis by preventing p21-dependent senescence in neural stem cells. Cell reports 26 34469723
2020 Effect of estrogen-active compounds on the expression of RACK1 and immunological implications. Archives of toxicology 25 32328699
2020 Ribosomes as a nexus between translation and cancer progression: Focus on ribosomal Receptor for Activated C Kinase 1 (RACK1) in breast cancer. British journal of pharmacology 25 32726469
2017 Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence. International journal of molecular sciences 25 28684670
2023 TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. Cell death & disease 24 37591850
2017 Transcriptional regulation of RACK1 and modulation of its expression: Role of steroid hormones and significance in health and aging. Cellular signalling 24 28192162
2017 GNB2L1 and its O-GlcNAcylation regulates metastasis via modulating epithelial-mesenchymal transition in the chemoresistance of gastric cancer. PloS one 24 28797110
2006 RACK1 is a BKCa channel binding protein. American journal of physiology. Cell physiology 24 17166942
2018 Hijacking a host scaffold protein, RACK1, for replication of a plant RNA virus. The New phytologist 23 30169907
2019 RACK1 interaction with c-Src is essential for osteoclast function. Experimental & molecular medicine 22 31358728
2016 Role of androgens in dhea-induced rack1 expression and cytokine modulation in monocytes. Immunity & ageing : I & A 22 27239218
2013 RACK1 promotes prostate cancer cell proliferation, invasion and metastasis. Molecular medicine reports 22 23912224
2023 Scaffold protein RACK1 regulates BR signaling by modulating the nuclear localization of BZR1. The New phytologist 20 37301989
2022 Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1. Cells 20 36010666
2022 Effects of endocrine disrupting chemicals on the expression of RACK1 and LPS-induced THP-1 cell activation. Toxicology 20 36113621
2017 The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1. Cellular signalling 20 28267599
2014 RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans. Cell cycle (Georgetown, Tex.) 20 24776851
2018 Ribosomal RACK1 promotes proliferation of neuroblastoma cells independently of global translation upregulation. Cellular signalling 19 30287278
2018 RACK1 attenuates RLR antiviral signaling by targeting VISA-TRAF complexes. Biochemical and biophysical research communications 19 30527812
2024 A novel Trichinella spiralis serine proteinase disrupted gut epithelial barrier and mediated larval invasion through binding to RACK1 and activating MAPK/ERK1/2 pathway. PLoS neglected tropical diseases 18 38190388
2022 CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway. Cell communication and signaling : CCS 18 35101055
2021 Roles of RACK1 in centrosome regulation and carcinogenesis. Cellular signalling 18 34843916
2025 RACK1 MARylation regulates translation and stress granules in ovarian cancer cells. The Journal of cell biology 17 39760726
2021 Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1. PLoS genetics 17 34214075
2022 Hepatic RACK1 deficiency protects against fulminant hepatitis through myeloid-derived suppressor cells. Theranostics 16 35265209
2022 Effects of endocrine active contaminating pesticides on RACK1 expression and immunological consequences in THP-1 cells. Environmental toxicology and pharmacology 16 36084878
2020 Morphine-induced RACK1-dependent autophagy in immortalized neuronal cell lines. British journal of pharmacology 16 31747048
2020 Dual functions of Rack1 in regulating Hedgehog pathway. Cell death and differentiation 15 32467643
2013 Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth. The American journal of pathology 15 23313748
2024 The c-Abl-RACK1-FAK signaling axis promotes renal fibrosis in mice through regulating fibroblast-myofibroblast transition. Cell communication and signaling : CCS 14 38689280
2023 Substrate-dependent interaction of SPOP and RACK1 aggravates cardiac fibrosis following myocardial infarction. Cell chemical biology 14 37442135
2022 RACK1 Regulates Poxvirus Protein Synthesis Independently of Its Role in Ribosome-Based Stress Signaling. Journal of virology 14 36098514
2021 GNA14's interaction with RACK1 inhibits hepatocellular carcinoma progression through reducing MAPK/JNK and PI3K/AKT signaling pathway. Carcinogenesis 14 34657150
2017 RACK1 promotes radiation resistance in esophageal cancer via regulating AKT pathway and Bcl-2 expression. Biochemical and biophysical research communications 14 28760343
2015 RACK1-mediated translation control promotes liver fibrogenesis. Biochemical and biophysical research communications 14 26002467
2012 RACK1 downregulation suppresses migration and proliferation of neuroblastoma cell lines. Oncology reports 14 22246531
2009 Depletion of WRN protein causes RACK1 to activate several protein kinase C isoforms. Oncogene 14 19966859
2024 OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination. Cellular oncology (Dordrecht, Netherlands) 13 38315284

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