Affinage

RACK1

Small ribosomal subunit protein RACK1 · UniProt P63244

Length
317 aa
Mass
35.1 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RACK1 is a seven-bladed WD40 β-propeller scaffold protein that functions as a stoichiometric component of the 40S ribosomal subunit and as a versatile cytoplasmic signaling adaptor, integrating kinase signaling with translation, quality control, innate immunity, cell adhesion, and developmental patterning. On the ribosome, RACK1 recruits PKCβII to phosphorylate eIF4E for cap-dependent translation of growth factors, mediates miRISC association with translating ribosomes for miRNA-dependent gene silencing, and regulates ribosome-associated quality control by promoting ubiquitylation of RPS2/RPS3/RPS20 at stalled ribosomes; its ribosomal residence is further modulated by PARP14-mediated MARylation, which redirects RACK1 into stress granules (PMID:15577927, PMID:22653060, PMID:21525958, PMID:28132843, PMID:39760726). Off the ribosome, RACK1 co-translocates with activated PKC isoforms to membranes, inhibits Src kinase at G1 and mitotic checkpoints to control cell cycle progression and E-cadherin stability, bridges MKK6 into the TRAF6–TAK1 complex for p38 MAPK activation, scaffolds NR2B–Fyn to suppress NMDA receptor phosphorylation, promotes NLRP3 inflammasome assembly, and regulates Hedgehog and planar cell polarity signaling (PMID:10480917, PMID:15254245, PMID:26038599, PMID:11943848, PMID:33207200, PMID:32467643, PMID:21262816). RACK1 stability and partner selectivity are governed by diverse post-translational modifications including O-GlcNAcylation at Ser122, Src-mediated Tyr228/246 phosphorylation, AMPK-mediated Thr50 phosphorylation, PCAF-mediated acetylation at K130, and ubiquitination by multiple E3 ligases (RAB40C, SMURF2, SPOP, TRIM26) (PMID:29454068, PMID:12400005, PMID:34348973, PMID:37828084, PMID:30112187).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Establishing that RACK1 is not a static anchor but a dynamic shuttling scaffold that co-translocates with activated PKC to specific subcellular sites answered the foundational question of how PKC reaches its substrates in living cells.

    Evidence Live-cell imaging and co-immunoprecipitation tracking PKC–RACK1 co-movement in CHO and NG108-15 cells

    PMID:10480917

    Open questions at the time
    • Identity of cargo-specific determinants driving differential translocation
    • Whether RACK1 shuttles all PKC isoforms or is selective
  2. 2002 High

    Demonstrating that RACK1 scaffolds the NMDA receptor NR2B subunit and Fyn kinase to suppress receptor phosphorylation and currents established RACK1 as an inhibitory adaptor in synaptic signaling, not merely a PKC shuttle.

    Evidence Co-immunoprecipitation, peptide disruption, and electrophysiology in CA1 hippocampal slices

    PMID:11943848

    Open questions at the time
    • Whether ethanol-induced dissociation of RACK1–Fyn is the sole mechanism for NR2B hyperphosphorylation
    • Structural basis of the ternary complex
  3. 2002 High

    Identifying Src as a kinase that phosphorylates RACK1 at Tyr228/246 and showing this creates an SH2-binding site revealed a reciprocal regulatory loop—RACK1 inhibits Src, but Src modifies RACK1 to alter its own partner recruitment.

    Evidence In vitro kinase assays and Tyr-to-Phe mutagenesis with in vivo phosphorylation validation

    PMID:12400005

    Open questions at the time
    • Whether Tyr228 and Tyr246 are phosphorylated independently or sequentially
    • Phosphatase(s) responsible for dephosphorylation
  4. 2003 High

    Localizing RACK1 to nascent focal complexes and showing that the Src-binding Y246 residue is required for integrin-mediated adhesion and chemotaxis connected RACK1's kinase-regulatory activity to cell migration.

    Evidence GFP-RACK1 live imaging, Y246F mutagenesis, and chemotaxis assays in CHO-K1 cells

    PMID:12589061

    Open questions at the time
    • Whether RACK1 regulates integrin inside-out signaling or only outside-in
    • How RACK1 is recruited to nascent versus mature adhesions
  5. 2004 High

    Multiple discoveries in 2004 collectively repositioned RACK1 from a PKC-specific adaptor to a central signaling hub: cryo-EM showed it is a stoichiometric 40S ribosomal subunit component that recruits PKC to phosphorylate eIF6 and stimulate translation; epistasis experiments demonstrated RACK1-mediated PKC phosphorylation of JNK Ser129 as a priming step for JNK activation; and cell-cycle analyses revealed RACK1 suppresses Src at G1 to delay S-phase entry.

    Evidence Cryo-EM localization on the 40S subunit, in vitro kinase assays with JNK Ser129 mutagenesis, Src inhibitor epistasis for G1/S control

    PMID:15184885 PMID:15254245 PMID:15577927 PMID:16061178

    Open questions at the time
    • Whether ribosomal and signaling functions are simultaneously active or mutually exclusive
    • Structural basis of RACK1's Src-inhibitory mechanism
  6. 2006 High

    Extending cell-cycle analysis to mitosis showed RACK1 suppresses Src at both G1 and mitotic checkpoints and maintains CDK1–cyclin B activity, broadening its role to a general checkpoint regulator.

    Evidence RACK1 overexpression/depletion with cell-cycle analysis and Sam68 phosphorylation readout in colon cells

    PMID:17072338

    Open questions at the time
    • Direct structural evidence for RACK1 inhibiting Src catalytic activity versus sequestering substrates
  7. 2008 High

    The 2.1 Å crystal structure of yeast RACK1/Asc1p confirmed the seven-bladed β-propeller fold and identified the conserved charged face mediating 40S binding; ribosome-binding-deficient mutants phenocopied full deletion, proving RACK1 functions from its ribosomal position.

    Evidence X-ray crystallography, structure-guided mutagenesis, polysome fractionation in S. cerevisiae

    PMID:19114558

    Open questions at the time
    • Human RACK1 structure on the ribosome at comparable resolution
    • How ribosome-bound RACK1 simultaneously engages cytoplasmic signaling partners
  8. 2010 High

    Discovering nuclear RACK1 at the BDNF promoter IV, where it displaces MeCP2 and promotes H4 acetylation, revealed a chromatin-regulatory function distinct from its cytoplasmic scaffolding roles.

    Evidence ChIP at BDNF promoter IV, co-immunoprecipitation with histones H3/H4, siRNA knockdown, reporter assays

    PMID:20410295

    Open questions at the time
    • How RACK1 is imported into the nucleus
    • Whether RACK1 regulates other gene promoters beyond BDNF
  9. 2011 High

    Three concurrent advances expanded RACK1's functional repertoire: it was shown to recruit miRISC/Argonaute to translating ribosomes for miRNA-mediated silencing, to interact with Vangl2 for planar cell polarity and convergent extension in zebrafish, and to stabilize E-cadherin at cell junctions by preventing Src-mediated ubiquitination via Hakai.

    Evidence Polysome fractionation with miRNA reporters in C. elegans and mammals; zebrafish morpholino knockdown with PCP phenotyping; calcium-switch and HGF-scatter assays with E-cadherin endocytosis readout

    PMID:21262816 PMID:21525958 PMID:21685945

    Open questions at the time
    • Whether miRISC recruitment requires the same RACK1 surface as PKC binding
    • How Vangl2 interaction is coordinated with ribosomal occupancy
  10. 2012 High

    Demonstrating that ribosome-bound RACK1 couples PKCβII to eIF4E phosphorylation for selective translation of growth/survival mRNAs provided a direct mechanistic link between RACK1's ribosomal location and oncogenic translation in hepatocellular carcinoma.

    Evidence Ribosome fractionation, PKCβII inhibitor epistasis, eIF4E knockdown, in vivo HCC models

    PMID:22653060

    Open questions at the time
    • Full catalog of mRNAs preferentially translated via this axis
    • Whether this mechanism operates in normal hepatocytes or is cancer-specific
  11. 2015 High

    Identifying RACK1 as the bridge that brings MKK6 into the TRAF6–TAK1 complex for selective p38 MAPK activation upon RANKL stimulation explained how pathway specificity is achieved in osteoclast differentiation.

    Evidence Reciprocal co-immunoprecipitation plus in vivo RANKL-induced bone loss model with RACK1 siRNA

    PMID:26038599

    Open questions at the time
    • Whether RACK1 similarly bridges MKK3 or is strictly MKK6-selective
    • Structural basis of the quaternary complex
  12. 2017 High

    Showing that RACK1 promotes ubiquitylation of RPS2, RPS3, and RPS20 on stalled ribosomes, parallel to ZNF598-mediated RPS10/RPS20 ubiquitylation, established RACK1 as a key component of mammalian ribosome-associated quality control (RQC).

    Evidence Quantitative ubiquitin proteomics, ubiquitination-site mutagenesis, poly(A)-stall reporter assays

    PMID:28132843

    Open questions at the time
    • Whether RACK1 itself recruits the E3 ligase or acts as the platform for collision sensing
    • Mechanism distinguishing transient pauses from pathological stalls
  13. 2018 High

    Mapping O-GlcNAcylation at Ser122 and showing it enhances RACK1 stability, ribosome binding, and PKCβII-mediated eIF4E phosphorylation—validated in knock-in mice—revealed a nutrient-sensing post-translational switch that tunes RACK1's translational output.

    Evidence Mass spectrometry, Ser122 knock-in mice, ribosome fractionation, in vivo HCC tumorigenesis

    PMID:29454068

    Open questions at the time
    • Identity of the OGT recruitment mechanism to RACK1
    • Whether O-GlcNAcylation and Tyr228/246 phosphorylation are coordinated
  14. 2019 High

    Single-molecule fluorescence showed RACK1 stably resides on human ribosomes for hours yet can readily exchange, resolving the question of whether RACK1 is a permanent or dynamic ribosomal constituent.

    Evidence Single-molecule fluorescence and bulk biochemical assays with engineered labeled human ribosomes

    PMID:31023766

    Open questions at the time
    • What triggers RACK1 exchange in vivo
    • Whether exchange rate changes under stress
  15. 2020 High

    RACK1 was established as an essential scaffolding component of the NLRP3 inflammasome: it binds NLRP3 and NEK7 to promote inflammasome assembly and caspase-1 activation, and a ribosome-binding mutant showed this function is separable from ribosomal roles; additionally, M. tuberculosis protein EST12 exploits RACK1 to recruit UCHL5 for K48-deubiquitination of NLRP3, activating pyroptosis.

    Evidence Co-immunoprecipitation, ribosome-binding separation-of-function mutant, NLRP3 inflammasome activity assays, EST12 crystal structure, in vivo infection models

    PMID:33097533 PMID:33207200

    Open questions at the time
    • Whether RACK1's inflammasome role is restricted to NLRP3 or extends to other inflammasome sensors
    • Structural model of the RACK1–NLRP3–NEK7 interface
  16. 2020 High

    Demonstrating dual context-dependent roles in Hedgehog signaling—promoting Ci proteolysis in the absence of Hh and facilitating Smo deubiquitination via Usp8 in the presence of Hh—showed RACK1 can switch between opposing signaling outcomes depending on ligand status.

    Evidence Genetic epistasis in Drosophila, co-immunoprecipitation, ubiquitination assays, mammalian conservation experiments

    PMID:32467643

    Open questions at the time
    • What triggers Rack1 dissociation from the Ci–Cos2 complex upon Hh stimulation
    • Whether this switch involves post-translational modification of RACK1
  17. 2021 High

    Identifying AMPK-mediated phosphorylation at Thr50 as a mechanism by which RACK1 suppresses type I interferon production (by sequestering IRF3/7 from phosphorylation) revealed RACK1 as a metabolic checkpoint in antiviral innate immunity.

    Evidence Kinase assays, Thr50 mutagenesis, IFN reporter assays, myeloid RACK1-KO mice

    PMID:34348973

    Open questions at the time
    • Whether RACK1 Thr50 phosphorylation is reversed by a specific phosphatase
    • Interplay between AMPK-mediated and NLRP3-activating functions of RACK1
  18. 2023 High

    Multiple E3 ligases (SMURF2, SPOP/CUL3, TRIM26) and a counteracting acetyltransferase (PCAF at K130) were shown to control RACK1 protein levels in distinct tissue contexts (ovarian cancer, cardiac fibrosis, osteosarcoma), establishing that RACK1 abundance is a regulated signaling variable rather than a constitutive constant.

    Evidence In vitro ubiquitination reconstitution (SMURF2), Co-IP with SPOP/TRIM26, mutagenesis, in vivo tumor and MI models with RACK1 rescue

    PMID:37442135 PMID:37591850 PMID:37828084

    Open questions at the time
    • Hierarchy or competition among the multiple E3 ligases targeting RACK1
    • Whether these ubiquitin modifications also regulate ribosome occupancy
  19. 2025 High

    Discovery that PARP14 MARylates RACK1 to drive stress granule assembly and that TARG1 reverses this modification to restore translation identified a writer/eraser system controlling RACK1's partitioning between active ribosomes and stress granules.

    Evidence MS-mapped MARylation sites, PARP14 inhibitor, TARG1 functional assays, polysome profiling, stress granule imaging, in vivo tumor models

    PMID:39760726

    Open questions at the time
    • Specific MARylation sites on RACK1
    • Whether MARylation and O-GlcNAcylation compete for RACK1 regulation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and regulatory model explaining how RACK1 partitions between ribosomal, cytoplasmic signaling, nuclear, and stress granule pools—and how its numerous post-translational modifications are hierarchically coordinated—remains unresolved.
  • No high-resolution structure of human RACK1 simultaneously engaged with a signaling partner on the ribosome
  • Quantitative accounting of RACK1 distribution across subcellular pools in a single cell type
  • Systematic mapping of PTM cross-talk (O-GlcNAc, phosphorylation, ubiquitination, MARylation, acetylation)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005829 cytosol 4 GO:0005840 ribosome 4 GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9612973 Autophagy 1
Partners
ATG5FYNGRIN2BNLRP3PRKCBSRCTRAF6VANGL2
Complex memberships
40S ribosomal subunitNLRP3 inflammasomeTRAF6–TAK1–MKK6 complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RACK1 acts as a PKC shuttling protein: upon PKC activation, RACK1 undergoes intracellular relocalization and co-moves with activated βIIPKC to the same subcellular sites, and this co-movement requires prior association of the two proteins. In situ co-immunoprecipitation, live-cell imaging, subcellular fractionation in CHO cells and NG108-15 cells transfected with dopamine D2L receptor The Journal of biological chemistry High 10480917
2002 RACK1 binds both the NR2B subunit of the NMDA receptor and the tyrosine kinase Fyn, forming an inhibitory scaffold complex that suppresses Fyn-mediated phosphorylation of NR2B and decreases NMDA receptor-mediated currents in CA1 hippocampal slices. Co-immunoprecipitation, peptide disruption assays, electrophysiology in hippocampal slices 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 (in the sixth WD repeat), and Src activity is required for RACK1 tyrosine phosphorylation and for RACK1 binding to Src's SH2 domain following PKC activation. In vitro kinase assays, site-directed mutagenesis of RACK1 tyrosines, in vivo phosphorylation with kinase-active/inactive Src mutants Oncogene High 12400005
2003 RACK1 localizes to a subset of nascent focal complexes in areas of cell protrusion and regulates integrin-mediated adhesion, cell protrusion, and chemotactic migration through its Src-binding site (Tyr246); a point mutant RACK1-Y246F that cannot bind Src fails to rescue these functions. GFP-tagged RACK1 live imaging, focal adhesion morphology screen, chemotaxis assays in CHO-K1 cells, site-directed mutagenesis Molecular biology of the cell High 12589061
2004 RACK1 serves as an adaptor for PKC-mediated JNK activation: RACK1 mediates phosphorylation of JNK on Ser129 by PKC, which augments subsequent MKK4/MKK7-mediated JNK phosphorylation. This pathway is required for JNK activation by TPA, TNFα, UV, and PKC but not by anisomycin or MEKK1. siRNA knockdown, in vitro kinase assays, site-directed mutagenesis of JNK Ser129, epistasis analysis Molecular cell High 16061178
2004 RACK1 binds inositol 1,4,5-trisphosphate receptors (IP3Rs) and enhances IP3R binding affinity for IP3, thereby mediating agonist-induced Ca2+ release from intracellular stores without affecting Ca2+ entry. Co-immunoprecipitation, RNAi knockdown, overexpression, Ca2+ imaging Proceedings of the National Academy of Sciences of the United States of America High 14983009
2004 RACK1 is a stoichiometric component of the eukaryotic 40S ribosomal subunit (localized to the head region near the mRNA exit channel by cryo-EM) and recruits activated PKC to the ribosome, leading to phosphorylation of eIF6 and stimulation of translation. Cryo-electron microscopy structural localization, biochemical fractionation, kinase assay EMBO reports High 15577927
2004 RACK1 regulates G1/S cell cycle progression by suppressing Src kinase activity at the G1 checkpoint; RACK1 overexpression inhibits Src-mediated Vav2, Rho GTPases, Stat3, and Myc, resulting in suppression of cyclin D1, CDK4, CDK2 and activation of p27 and Rb, delaying G1/S. RACK1 overexpression, siRNA knockdown, epistasis with Src inhibitors and dominant-negative constructs in NIH 3T3 and colon cells Molecular and cellular biology High 15254245
2004 RACK1 regulates Src-mediated phosphorylation of Sam68 and p190RhoGAP; the βIIPKC–RACK1 association is required for Src phosphorylation of RACK1; RACK1 inhibits Src-mediated p190RhoGAP signaling and actin cytoskeleton rearrangement. Cell-permeable peptides disrupting RACK1-βIIPKC interaction, in vitro kinase assays, phosphorylation assays Oncogene High 15184885
2006 RACK1 inhibits growth of colon cells by suppressing Src activity at G1 and mitotic checkpoints; mechanistically, RACK1 suppresses Src-mediated Sam68 phosphorylation and maintains the CDK1-cyclin B complex in an active state to regulate mitotic exit. RACK1 overexpression, Src or RACK1 depletion, cell-permeable peptides, cell cycle analysis Oncogene High 17072338
2007 RACK1 regulates paxillin dynamics at focal complexes during cell migration via its Src-binding site: RACK1-deficient cells show reduced paxillin and talin dynamics and enhanced Src activity; wild-type RACK1 but not RACK1-Y246F rescues these defects and regulates Src-mediated phosphorylation of paxillin at Tyr31/118. RACK1 knockout cells, GFP-paxillin FRAP, siRNA, RACK1-Y246F mutant rescue experiments Experimental cell research High 17574549
2008 The crystal structure of yeast RACK1 (Asc1p) at 2.1 Å resolution reveals a seven-bladed β-propeller; conserved charged residues on one face mediate 40S ribosome binding, and disruption of ribosome binding mimics phenotypes of RACK1 deletion and impairs Scp160 association with translating ribosomes, demonstrating that RACK1 functions from its ribosomal position. X-ray crystallography (2.1 Å), structure-guided mutagenesis, polysome fractionation, genetic phenotyping in S. cerevisiae Molecular and cellular biology High 19114558
2010 Nuclear RACK1 mediates epigenetic regulation of BDNF gene expression: following cAMP pathway activation, RACK1 associates with histones H3 and H4 at the BDNF promoter IV, promotes dissociation of the transcriptional repressor MeCP2, and leads to H4 acetylation and promoter IV-specific BDNF transcription. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, siRNA knockdown, promoter reporter assays The Journal of biological chemistry High 20410295
2011 RACK1 binds to the VEGF receptor Flt1 and mediates VEGF/Flt1-dependent cell migration via activation of PI3K/Akt and Rac1 pathways; RNAi-mediated RACK1 depletion markedly suppresses VEGF-driven migration without affecting proliferation. In vitro binding assay, RNA interference, PI3K/Akt pathway analysis, migration assays The Journal of biological chemistry Medium 21212275
2011 RACK1 is required for the association of the miRNA-induced silencing complex (miRISC) with translating ribosomes; RACK1 interacts directly with Argonaute components of miRISC in nematodes and mammals, and alteration of RACK1 expression impairs miRNA-mediated gene repression in both systems. Co-immunoprecipitation, polysome fractionation, in vivo miRNA reporter assays in C. elegans and mammalian cells EMBO reports High 21525958
2011 Rack1 interacts with Vangl2 (vertebrate Vang/planar cell polarity protein) and is required for Vangl2 membrane localization; Rack1 knockdown in zebrafish disrupts oriented cell division, cellular polarization, and convergent extension; Rack1 also antagonizes canonical Wnt signaling. Yeast two-hybrid, co-immunoprecipitation, zebrafish morpholino knockdown, dominant-negative constructs Proceedings of the National Academy of Sciences of the United States of America High 21262816
2011 Rack1 inhibits Src activity to stabilize E-cadherin at cell-cell contacts by preventing Src-mediated phosphorylation and ubiquitination of E-cadherin by the E3 ligase Hakai, and by blocking Src-dependent endocytosis of E-cadherin, thereby promoting epithelial cell-cell adhesion. siRNA knockdown, RACK1 overexpression, calcium switch assay, HGF-induced scatter assay, E-cadherin endocytosis assays Oncogene High 21685945
2012 Ribosomal RACK1 couples with PKCβII to promote phosphorylation of eIF4E, leading to preferential cap-dependent translation of growth and survival factors; this mechanism underlies RACK1-mediated chemoresistance and growth in hepatocellular carcinoma. Ribosome fractionation, co-immunoprecipitation, PKCβII inhibition, eIF4E knockdown, in vitro and in vivo tumor models The Journal of clinical investigation High 22653060
2012 RACK1 acts as a ribosomal scaffold protein for the β-actin mRNA/ZBP1 complex on ribosomes; RACK1's Src phosphorylation site (Y246) is required for its binding to the ZBP1/β-actin mRNA complex, contributing to ZBP1 release from mRNA and subsequent β-actin translation. Co-immunoprecipitation, RNA immunoprecipitation, site-directed mutagenesis of Y246, polysome analysis in neurons PloS one Medium 22523568
2015 RACK1 mediates RANKL-dependent selective activation of p38 MAPK in osteoclast precursors by acting as a bridge that brings MKK6 into the TRAF6-TAK1 signaling complex; RACK1 interacts with RANK, TRAF6, TAK1, and MKK6 upon RANKL stimulation. Co-immunoprecipitation, siRNA knockdown, in vivo RANKL-induced bone loss model with RACK1 siRNA administration Science signaling High 26038599
2016 RACK1 interacts with ATG5 and is required for autophagy activation; classical autophagy inducers (starvation, mTOR blockade) stimulate RACK1-ATG5 interaction, and prevention of this interaction by mutagenesis blocks autophagosome formation. Co-immunoprecipitation, GST pulldown, mutagenesis, autophagy flux assays (LC3-II, p62), siRNA knockdown The Journal of biological chemistry High 27325703
2017 ZNF598 and RACK1 regulate mammalian ribosome-associated quality control (RQC) of stalled ribosomes: ZNF598 primarily mediates ubiquitylation of RPS10 and RPS20, while RACK1 regulates ubiquitylation of RPS2, RPS3, and RPS20; these modifications are required for resolution of poly(A)-induced ribosome stalls. Mass spectrometry-based ubiquitin profiling, mutagenesis blocking ubiquitylation sites, reporter assays for stall readthrough, gain/loss of ZNF598 and RACK1 function Molecular cell High 28132843
2018 RACK1 is O-GlcNAcylated at Ser122, which enhances its protein stability, ribosome binding affinity, and interaction with PKCβII, leading to increased eIF4E phosphorylation and translation of oncogenes; genetic ablation of Ser122 O-GlcNAcylation suppresses HCC tumorigenesis in a knock-in mouse model. Mass spectrometry mapping, transgenic knock-in mice, co-immunoprecipitation, ribosome fractionation, in vitro and in vivo tumor assays Journal of hepatology High 29454068
2018 UBE2T promotes RACK1 ubiquitination and proteasomal degradation at lysine residues K172, K225, and K257 independently of an E3 ligase, activating Wnt/β-catenin signaling in gastric cancer. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis of RACK1 lysines, in vitro and in vivo tumor models Oncogene Medium 33323973
2019 RAB40C is the E3 ubiquitin ligase responsible for RACK1 ubiquitination; RAB40C-mediated control of RACK1 protein levels is important for cancer cell growth and T-cell migration. siRNA screen, co-immunoprecipitation, ubiquitination assay, functional migration and growth assays Future science OA Medium 30112187
2019 RACK1 directly binds Nanog, preventing its interaction with E3 ubiquitin ligase FBXW8 and thereby blocking ubiquitin-dependent proteasomal degradation of Nanog; this interaction promotes cancer stem cell self-renewal and chemoresistance in HCC. Co-immunoprecipitation, ubiquitination assay, mutagenesis, sphere formation and in vivo tumor assays Theranostics Medium 30809310
2019 RACK1 stably associates with the human ribosome and displays limited conformational dynamics; fluorescently labeled RACK1 remains bound for hours in vitro but readily reassociates with the ribosome upon exchange. Single-molecule fluorescence, bulk biochemical assays, engineered fluorescently labeled human ribosomes RNA (New York, N.Y.) High 31023766
2020 RACK1 is a component of NLRP3 inflammasome complexes in macrophages; RACK1 interacts with NLRP3 and NEK7 (but not ASC) and promotes the active conformation of NLRP3 required for inflammasome assembly; suppression of RACK1 abrogates caspase-1 activation and IL-1β release specifically in response to NLRP3-activating stimuli. Co-immunoprecipitation, siRNA knockdown, caspase-1 activity assay, IL-1β ELISA, ribosome-binding mutant of RACK1 Cell reports High 33207200
2020 RACK1 acts as an endogenous host sensor recruited by Mycobacterium tuberculosis protein EST12; the EST12-RACK1 complex recruits deubiquitinase UCHL5 to promote K48-linked deubiquitination of NLRP3, leading to NLRP3 inflammasome activation, gasdermin D-mediated pyroptosis, and IL-1β secretion. Co-immunoprecipitation, crystal structure of EST12, site-directed mutagenesis (EST12 Y80), ubiquitination assays, in vitro and in vivo infection models Science advances High 33097533
2020 Poxvirus phosphorylation of RACK1 at Ser278 (mimicking negative charge) alters the swivel motion of the 40S head domain, confers resistance to protein synthesis inhibitors, and broadly supports non-canonical translation modes including poly(A) leader-dependent translation. Phosphomimetic mutagenesis, ribosome structural analysis, translation reporter assays, drug resistance assays Cell reports High 34496247
2021 RACK1 interacts with BRCA1 and is required for proper centrosomal localization of BRCA1 and regulation of centrosome number; RACK1 also directly binds PLK1 and Aurora A, promotes PLK1 phosphorylation via Aurora A, and overexpression of RACK1 causes centrosome amplification through PLK1 overactivation leading to premature centriole disengagement. Co-immunoprecipitation, direct binding assays, centrosome counting, PLK1 kinase activity assay, RACK1 overexpression Cellular signalling Medium 34843916
2021 RACK1 is required for flavivirus (ZIKV, DENV, WNV, POWV) replication organelle (vesicle packet) biogenesis; RACK1 interacts with NS1 proteins from multiple flaviviruses, and its loss alters viral replication factory morphology. CRISPR genome-wide screen, siRNA, co-immunoprecipitation with NS1, electron microscopy of replication factories Journal of virology High 34586867
2021 AMPK phosphorylates RACK1 at Thr50 upon viral infection, which enhances RACK1's interaction with IRF3/7 and inhibits IRF3/7 phosphorylation, thereby suppressing type I interferon production. Co-immunoprecipitation, site-directed mutagenesis of Thr50, kinase assays, IFN reporter assays, myeloid RACK1-KO mice Journal of immunology High 34348973
2022 RACK1, as part of the DENV replication complex, recruits RNA-binding proteins Vigilin and SERBP1 to the 40S ribosomal subunit; Vigilin and SERBP1 interact with DENV genomic RNA, and their binding to RACK1 is required for efficient viral RNA translation and replication. RACK1 interactome by mass spectrometry, siRNA screen, RNA immunoprecipitation, Vigilin/SERBP1 mutants lacking RACK1-binding domain Journal of virology High 35266803
2023 SMURF2 is an E3 ubiquitin ligase for RACK1 that adds K6, K33, and K48 ubiquitin chains promoting RACK1 degradation; PCAF-mediated acetylation of RACK1 at K130 inhibits SMURF2-mediated ubiquitination and promotes RACK1 stability in ovarian cancer. Co-immunoprecipitation, in vitro ubiquitination assay, mass spectrometry, mutagenesis, in vivo tumor models Cell death and differentiation High 37828084
2023 SPOP (CUL3 adaptor E3 ligase) binds RACK1 at Ser/Thr-rich motifs and induces RACK1 ubiquitination and degradation, reducing RACK1-mediated suppression of Smad3 signaling and promoting cardiac fibroblast activation and fibrosis. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function in cardiac fibroblasts and MI mouse model, RACK1 rescue experiments Cell chemical biology High 37442135
2023 TRIM26 interacts with RACK1 and promotes its proteasomal degradation, thereby inactivating MEK/ERK signaling and inhibiting osteosarcoma progression; RACK1 overexpression rescues TRIM26-induced suppression of p-MEK/p-ERK. Co-immunoprecipitation, gain/loss-of-function, ubiquitination assays, western blot for MEK/ERK phosphorylation Cell death & disease Medium 37591850
2023 FMRP regulates RACK1 protein levels in human/macaque neurons via interaction with CNOT1 (an mRNA deadenylase complex component); reduced RACK1 caused by FMRP deficiency leads to mitochondrial dysfunction and neuronal hyperexcitability resembling fragile X syndrome. Multiomics (RNA interactome, protein interactome), RACK1 genetic reduction, human fetal cortical slice models, FXS patient iPSC-derived neurons Neuron Medium 37820724
2023 RACK1 stabilizes β-catenin in breast cancer by competitively binding PSMD2 (a proteasome component) and preventing ubiquitinated β-catenin from engaging PSMD2 for degradation, thereby activating canonical WNT signaling. Co-immunoprecipitation, competitive binding assays, proteasome degradation assays, in vitro and in vivo tumor models Cell death & disease Medium 37848434
2025 PARP14 MARylates RACK1, promoting stress granule formation and colocalization of RACK1 with G3BP1, eIF3η, and 40S ribosomal proteins in stress granules, while reducing translation of a subset of mRNAs including AKT; the ADP-ribosyl hydrolase TARG1 deMARylates RACK1 to dissociate stress granules and restore translation. Mass spectrometry identification of MARylation sites, site-directed mutagenesis, PARP14 inhibitor, TARG1 functional assays, polysome profiling, stress granule imaging, in vivo tumor models The Journal of cell biology High 39760726
2006 RACK1 localizes to focal adhesions together with NHE5, β1 integrin, paxillin, and vinculin; RACK1 directly binds NHE5 and positively regulates NHE5 transporter activity both through direct interaction and through an integrin-dependent pathway. Co-immunoprecipitation, dominant-negative RACK1 mutants, siRNA, NHE5 activity assay, co-localization by immunofluorescence Cellular signalling Medium 16920332
2006 RACK1 directly binds the intracellular C-terminal tail of the BKCa (large conductance Ca2+-activated K+) channel, co-localizes with BKCa in vascular smooth muscle cells, and affects BKCa biophysical properties. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunocytochemistry, electrophysiology American journal of physiology. Cell physiology Medium 17166942
2010 RACK1 promotes Bax oligomerization and disrupts the Bax-Bcl-XL interaction; RACK1 interacts with Bax through the BH3 domain both in vitro and in vivo; overexpression of RACK1 promotes UV-induced apoptosis while knockdown inhibits it. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation, Bax oligomerization assay, apoptosis assay Cellular signalling Medium 20541605
2007 RACK1 is required for apical expression of CFTR in airway epithelial cells: RACK1 forms a complex with PKCε, NHERF1, and tubulin; siRNA-mediated RACK1 knockdown reduces apical CFTR by ~87% without affecting total CFTR expression. siRNA knockdown, confocal microscopy, apical surface biotinylation, mass spectrometry, in vitro binding assays American journal of physiology. Cell physiology High 17409124
2002 RACK1 mediates translocation of activated PKCα to the plasma membrane and modulation of integrin-associated signaling in chondrocyte mechanotransduction: mechanical stimulation induces β1 integrin-dependent translocation of PKCα and increased association of RACK1 with PKCα and β1 integrin. Western blotting, subcellular fractionation, co-immunoprecipitation, integrin-blocking antibodies and RGD peptides Osteoarthritis and cartilage Medium 12435334
2020 Rack1 plays dual roles in Hedgehog signaling: in the absence of Hh, Rack1 promotes Ci-Rack1-Cos2 complex formation leading to Slimb-mediated Ci proteolysis; in the presence of Hh, Rack1 dissociates from this complex and forms a trimeric complex with Smo and Usp8, promoting Smo deubiquitination and cell surface accumulation; this regulation is conserved from Drosophila to mammalian cells. Co-immunoprecipitation, genetic epistasis in Drosophila, mammalian cell rescue experiments, ubiquitination assays Cell death and differentiation High 32467643

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 368 21978545
2017 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation. Molecular cell 297 28132843
2004 Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome. EMBO reports 234 15577927
2004 RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction. The Journal of neuroscience : the official journal of the Society for Neuroscience 205 15548669
2020 RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma. Molecular oncology 181 31997535
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 155 11943848
1999 Coordinated movement of RACK1 with activated betaIIPKC. The Journal of biological chemistry 154 10480917
2017 Roles for RACK1 in cancer cell migration and invasion. Cellular signalling 150 28336233
2008 Direct link between RACK1 function and localization at the ribosome in vivo. Molecular and cellular biology 129 19114558
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 122 22653060
2006 RACK1 mediates multiple hormone responsiveness and developmental processes in Arabidopsis. Journal of experimental botany 110 16829549
2010 Involvement of Arabidopsis RACK1 in protein translation and its regulation by abscisic acid. Plant physiology 106 21098678
2000 RACK1 is up-regulated in angiogenesis and human carcinomas. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 102 11099474
2020 Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1β immune pathway. Science advances 98 33097533
2018 O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis. Journal of hepatology 94 29454068
2002 RACK1: a novel substrate for the Src protein-tyrosine kinase. Oncogene 93 12400005
2011 RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. The Journal of biological chemistry 90 21212275
2020 A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. Oncogene 86 33323973
2004 RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release. Proceedings of the National Academy of Sciences of the United States of America 82 14983009
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 Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog. Theranostics 72 30809310
2019 RACK1 promotes the invasive activities and lymph node metastasis of cervical cancer via galectin-1. Cancer letters 70 31705928
2011 The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans. EMBO reports 67 21525958
2006 RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints. Oncogene 67 17072338
2004 RACK1 regulates G1/S progression by suppressing Src kinase activity. Molecular and cellular biology 67 15254245
2020 Endocrine-Disrupting Chemicals' (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1. International journal of molecular sciences 64 33287384
2020 RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly. Cell reports 62 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 56 19946739
2010 Epigenetic regulation of BDNF expression via the scaffolding protein RACK1. The Journal of biological chemistry 54 20410295
2018 RACK1 promotes tumorigenicity of colon cancer by inducing cell autophagy. Cell death & disease 53 30451832
2011 Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity. Proceedings of the National Academy of Sciences of the United States of America 53 21262816
2021 Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication. Journal of virology 50 34586867
2017 Structural analysis of ribosomal RACK1 and its role in translational control. Cellular signalling 50 28161490
2007 RACK1 regulates Src activity and modulates paxillin dynamics during cell migration. Experimental cell research 49 17574549
2000 The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1. European journal of biochemistry 46 10849009
2019 RACK1 on and off the ribosome. RNA (New York, N.Y.) 45 31023766
2015 The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors. Science signaling 45 26038599
2012 RACK1 is a ribosome scaffold protein for β-actin mRNA/ZBP1 complex. PloS one 45 22523568
2020 Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin. International journal of molecular sciences 44 32731602
2008 RACK1, a new ADAM12 interacting protein. Contribution to liver fibrogenesis. The Journal of biological chemistry 43 18621736
2002 Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction. Osteoarthritis and cartilage 42 12435334
2020 FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation. Journal of cellular and molecular medicine 39 32227589
2016 RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy. The Journal of biological chemistry 39 27325703
2021 PHB2 promotes tumorigenesis via RACK1 in non-small cell lung cancer. Theranostics 38 33537079
2011 Rack1 promotes epithelial cell-cell adhesion by regulating E-cadherin endocytosis. Oncogene 38 21685945
2015 RACK1, scaffolding a heterotrimeric G protein and a MAPK cascade. Trends in plant science 35 25986967
2017 RACK1 regulates neural development. Neural regeneration research 34 28852378
2004 RACK1 regulates Src-mediated Sam68 and p190RhoGAP signaling. Oncogene 34 15184885
1999 Structure and genomic organization of porcine RACK1 gene. Biochimica et biophysica acta 34 10673032
2006 RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity. Cellular signalling 33 16920332
2021 Effects of Bisphenols on RACK1 Expression and Their Immunological Implications in THP-1 Cells. Frontiers in pharmacology 31 34621174
2020 OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression. Oncogenesis 31 33311444
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
2006 Localization of the scaffolding protein RACK1 in the developing and adult mouse brain. Brain research 30 16414032
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 28 37225849
2023 Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression. Cell death and differentiation 28 37828084
2022 RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication. Journal of virology 28 35266803
2013 Up-regulation of RACK1 by TGF-β1 promotes hepatic fibrosis in mice. PloS one 28 23555900
2020 Ribosomal protein RACK1 enhances translation of poliovirus and other viral IRESs. Virology 27 32308198
2013 AChE and RACK1 promote the anti-inflammatory properties of fluoxetine. Journal of molecular neuroscience : MN 27 24258317
2023 Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. Neuron 25 37820724
2020 Effect of estrogen-active compounds on the expression of RACK1 and immunological implications. Archives of toxicology 25 32328699
2017 RACK1 is necessary for the formation of point contacts and regulates axon growth. Developmental neurobiology 25 28245531
2017 Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence. International journal of molecular sciences 24 28684670
2006 RACK1 is a BKCa channel binding protein. American journal of physiology. Cell physiology 24 17166942
2023 TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. Cell death & disease 23 37591850
2023 RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin. Cell death & disease 22 37848434
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
2018 Hijacking a host scaffold protein, RACK1, for replication of a plant RNA virus. The New phytologist 21 30169907
2009 Dissection of the relationship between RACK1 and heterotrimeric G-proteins in Arabidopsis. Plant & cell physiology 21 19651700
2006 RACK1, a novel hPER1-interacting protein. Journal of molecular neuroscience : MN 21 16757810
2023 Scaffold protein RACK1 regulates BR signaling by modulating the nuclear localization of BZR1. The New phytologist 20 37301989
2021 Negative charge in the RACK1 loop broadens the translational capacity of the human ribosome. Cell reports 20 34496247
2014 RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans. Cell cycle (Georgetown, Tex.) 20 24776851
2023 CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability. Oncogene 17 36658304
2022 CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway. Cell communication and signaling : CCS 17 35101055
2021 Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1. PLoS genetics 17 34214075
2021 Roles of RACK1 in centrosome regulation and carcinogenesis. Cellular signalling 17 34843916
2018 RAB40C regulates RACK1 stability via the ubiquitin-proteasome system. Future science OA 17 30112187
2013 RACK1 promoted the growth and migration of the cancer cells in the progression of esophageal squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 23893384
2010 RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl-XL. Cellular signalling 17 20541605
2007 Effects of RACK1 on cell migration and IGF-I signalling in cardiomyoctes are not dependent on an association with the IGF-IR. Cellular signalling 17 17900863
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 role of RACK1 in airway epithelial mesenchymal transition and apoptosis. Journal of cellular and molecular medicine 16 32064783
2021 RACK1 T50 Phosphorylation by AMPK Potentiates Its Binding with IRF3/7 and Inhibition of Type 1 IFN Production. Journal of immunology (Baltimore, Md. : 1950) 15 34348973
2020 Dual functions of Rack1 in regulating Hedgehog pathway. Cell death and differentiation 15 32467643
2007 Role of the scaffold protein RACK1 in apical expression of CFTR. American journal of physiology. Cell physiology 15 17409124
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
2012 RACK1 downregulation suppresses migration and proliferation of neuroblastoma cell lines. Oncology reports 14 22246531
2009 RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation. Biochemical and biophysical research communications 14 19785988
2025 RACK1 MARylation regulates translation and stress granules in ovarian cancer cells. The Journal of cell biology 13 39760726