Affinage

CCT2

T-complex protein 1 subunit beta · UniProt P78371

Round 2 corrected
Length
535 aa
Mass
57.5 kDa
Annotated
2026-04-28
61 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCT2 is a subunit of the TRiC/CCT chaperonin complex that folds obligate substrates including tubulin, actin, G-transducin β1, KRAS, Gli-1, and ALDOA in an ATP-dependent manner, and it moonlights as a ubiquitin-independent aggrephagy receptor for solid protein aggregates. When solid aggregates accumulate, CCT2 exits the TRiC complex as a monomer, exposing a non-classical VLIR motif that binds ATG8/LC3 family proteins; this receptor switch is positively regulated by Atg1-mediated phosphorylation at Ser412/Ser470 and by direct Atg11 binding, while LCA-causative mutations (T400P/R516H) impair ADP release and trap CCT2 in the closed complex, blocking both chaperone and aggrephagy functions (PMID:35366418, PMID:39322741, PMID:37644231). Compound heterozygous CCT2 mutations cause Leber congenital amaurosis through destabilization of the TRiC complex and depletion of retinal client proteins including Gβ1 and CCDC181 at photoreceptor connecting cilia (PMID:27645772, PMID:38830954). Beyond proteostasis, CCT2 promotes tumor progression by stabilizing oncoproteins such as KRAS and β-catenin, activating JAK2/STAT3 signaling, and suppressing anti-tumor immunity through inhibition of Ca²⁺-NFAT signaling in T cells (PMID:38582394, PMID:38165547, PMID:39079960, PMID:41288742).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2015 Medium

    Establishing that CCT2, as a TRiC subunit, is essential for cancer cell survival answered whether individual chaperonin subunits are rate-limiting in proliferating cells and linked CCT2 to oncogenic dependency.

    Evidence RNAi functional genetic screen and copy number analysis in breast cancer cell lines

    PMID:25704758

    Open questions at the time
    • Specific substrates mediating cancer cell essentiality were not identified
    • Whether CCT2 essentiality extends beyond breast cancer was untested
  2. 2016 High

    Discovery that compound heterozygous CCT2 mutations (T400P/R516H) cause Leber congenital amaurosis revealed that TRiC integrity is critical for retinal cell survival and that Gβ1 is a key retinal client protein whose depletion underlies disease pathogenesis.

    Evidence Biochemical stability assays, co-IP for CCTβ–CCTγ interaction, patient iPSC proliferation assays, rescue in 661W cells, immunostaining of mouse retina

    PMID:27645772

    Open questions at the time
    • Photoreceptor-specific versus retinal ganglion cell contributions to disease were unresolved
    • Whether partial TRiC disruption affects substrates beyond Gβ1 in retina was unknown
  3. 2018 High

    Genetic validation in zebrafish demonstrated that CCT2 loss of function causes retinal degeneration and impaired cell cycle progression, and human CCTβ RNA rescue confirmed functional conservation across vertebrates.

    Evidence CRISPR-Cas9 cct2 mutagenesis in zebrafish with RNA rescue, TUNEL and EdU assays

    PMID:29450543

    Open questions at the time
    • Which specific cell cycle regulators require CCT2 folding in retinal progenitors was not determined
    • Mechanism linking CCT2 to cell cycle regulation versus apoptosis not disentangled
  4. 2019 Medium

    Identification of Gli-1 as a CCT2 client under hypoxia expanded the repertoire of cancer-relevant substrates, showing CCT2 prevents β-TrCP-mediated ubiquitination and degradation of an oncogenic transcription factor.

    Evidence Mass spectrometry identification of CCT2–Gli-1 interaction, RNAi knockdown, xenograft colorectal cancer model

    PMID:31462707

    Open questions at the time
    • Direct in vitro folding assay for Gli-1 by CCT2 was not performed
    • Whether the interaction requires the intact TRiC complex or CCT2 monomers was unresolved
  5. 2019 Medium

    Demonstration that CCT2 stabilizes Cdc20 revealed a link between the TRiC chaperonin and cell cycle checkpoint control, as CCT2 depletion reduced Cdc20 levels and reversed virus-induced CDK4 degradation.

    Evidence siRNA depletion of CCT2/CCT5 with Cdc20 and CDK4 western blotting, apoptosis and cell cycle assays in MDRV-infected cells

    PMID:31282373

    Open questions at the time
    • Only tested in viral infection context; unclear if Cdc20 is a TRiC client in uninfected cells
    • Direct CCT2–Cdc20 physical interaction not shown
  6. 2020 Medium

    Finding that extracellular vesicle–delivered CCT2 suppresses CD4⁺ T cell activation through Ca²⁺-calcineurin-NFAT1 signaling established a non-chaperone immunomodulatory role for CCT2 in the extracellular compartment.

    Evidence Mass spectrometry of UC-MSC-derived EVs, liver IRI mouse model, flow cytometry for CD154, Ca²⁺-calcineurin-NFAT1 pathway analysis

    PMID:32999825

    Open questions at the time
    • Identity of the calcium channel regulated by CCT2 was not resolved
    • Whether CCT2 acts as monomer or oligomer in EVs was not determined
  7. 2022 High

    The landmark discovery that CCT2 functions as a ubiquitin-independent aggrephagy receptor fundamentally redefined CCT2 as a bifunctional protein: aggregate accumulation triggers CCT2 monomer release from TRiC, exposing a VLIR motif for ATG8 binding and selective clearance of solid (not liquid) aggregates.

    Evidence Co-IP, pulldown, live-cell imaging, VLIR motif mutagenesis, fractionation of solid vs. liquid aggregates, loss-of-function in cells and mouse brain

    PMID:35366418

    Open questions at the time
    • The structural basis for the monomer–oligomer switch was not resolved
    • Whether CCT2 aggrephagy is active in all cell types was not established
    • Signals triggering monomerization beyond aggregate accumulation were unknown
  8. 2023 High

    Kinetic analysis of LCA-causative CCT2 mutations revealed that T400P/R516H slows ADP off-rate, stabilizing the closed TRiC state and trapping CCT2 within the complex, thereby explaining how these mutations simultaneously impair both chaperonin cycling and aggrephagy receptor availability.

    Evidence Steady-state and transient kinetic ATPase assays on yeast TRiC carrying equivalent mutations, substrate-stimulated ATPase measurements

    PMID:37644231

    Open questions at the time
    • Whether the kinetic defect affects all TRiC substrates equally or selectively was untested
    • Structural detail of how mutations alter the ADP binding pocket was not determined
  9. 2024 High

    Elucidation of the regulatory mechanisms controlling CCT2 aggrephagy showed that Atg1-mediated phosphorylation (Ser412/Ser470) and direct Atg11 binding both promote CCT2–ATG8 interaction, providing the first upstream signaling pathway governing the chaperone-to-receptor switch.

    Evidence Phosphorylation site mutagenesis, in vivo phosphorylation assays, domain mapping of Atg11–Cct2 interaction, aggrephagy assays in yeast and mammalian cells

    PMID:39322741

    Open questions at the time
    • Mammalian kinase equivalent of Atg1 acting on CCT2 confirmed only for conservation, not fully characterized
    • Whether other post-translational modifications regulate the switch was unknown
  10. 2024 Medium

    Multiple studies converged to show CCT2 stabilizes diverse oncoproteins—KRAS via direct binding (confirmed by SPR), β-catenin via recruitment of the HSP105–PP2A dephosphorylation complex—and activates JAK2/STAT3 signaling, establishing CCT2 as a multi-pathway oncogenic chaperone.

    Evidence Co-IP, mass spectrometry, surface plasmon resonance for KRAS binding; co-IP for CCT2–β-catenin–HSP105–PP2A; JAK2/STAT3 pathway readouts with IL-6 rescue; xenograft models

    PMID:38165547 PMID:38582394 PMID:41789667

    Open questions at the time
    • Direct CCT2–STAT3 physical interaction was not demonstrated
    • Whether β-catenin stabilization requires TRiC or monomeric CCT2 is unknown
    • Structural basis for CCT2–KRAS interaction not resolved
  11. 2024 High

    Knock-in mouse models carrying LCA mutations confirmed retinal photoreceptor degeneration and identified CCDC181 as a new CCT2-interacting protein whose ciliary localization depends on functional CCT2, extending the disease mechanism to ciliary proteostasis.

    Evidence Cct2 knock-in mice (T400P/R516H), retinal histology, co-IP for CCTβ–CCDC181, immunostaining of connecting cilia

    PMID:38830954

    Open questions at the time
    • Whether CCDC181 mislocalization is sufficient to cause photoreceptor degeneration was not tested
    • Full inventory of ciliary substrates affected by CCT2 mutations was not determined
  12. 2024 Medium

    Viral exploitation studies revealed that PRRSV nsp3 hijacks CCT2's aggrephagy function to degrade MDA5 aggregates, and LASV matrix protein disrupts CCT2's cytoskeletal folding to block autophagosome–lysosome fusion, demonstrating that pathogens target both arms of CCT2 biology.

    Evidence Co-IP for MDA5–CCT2–nsp3 and LASV-Z–CCT2, mutagenesis of viral interaction sites, autophagy flux assays, VLP budding assays

    PMID:38272236 PMID:39007910

    Open questions at the time
    • Host factor specificity—whether other TRiC subunits are similarly exploited—was not compared
    • Relevance to in vivo viral pathogenesis in animal infection models not established
  13. 2025 Medium

    Discovery that CCT2 mRNA is m6A-modified by METTL3 downstream of histone lactylation revealed an epitranscriptomic axis controlling CCT2 protein levels in tumors, and elevated CCT2 suppresses CD8⁺ T cell cytotoxicity by inhibiting Ca²⁺ influx.

    Evidence ChIP for H3K18la at METTL3 locus, RIP for m6A on CCT2 mRNA, Ca²⁺ influx measurement, T cell cytotoxicity assay, homograft mouse model

    PMID:41288742

    Open questions at the time
    • Direct molecular target of CCT2 that mediates Ca²⁺ channel inhibition remains unidentified
    • Whether this regulatory axis operates in non-gastric cancers was untested
  14. 2026 Medium

    Identification of ALDOA as a direct CCT2 client linked chaperonin function to glycolytic reprogramming, while exosomal CCT2 was shown to polarize macrophages toward the immunosuppressive M2 phenotype, and CCT2 was separately identified as a cGAS-associated factor that attenuates cGAS-STING signaling through aggrephagy-mediated clearance of DNA-bound cGAS aggregates.

    Evidence Co-IP and GST pulldown for CCT2–ALDOA; ECAR, glucose uptake, lactate assays; exosome M2 polarization; photo-cross-linking proteomics for cGAS–CCT2; autophagy flux and STING signaling assays

    PMID:42003909 PMID:42043443

    Open questions at the time
    • Whether ALDOA folding requires full TRiC or monomeric CCT2 was not resolved
    • The exosomal CCT2 form (monomer vs. complex) acting on macrophages was not characterized
    • Whether cGAS aggregate clearance is specific to CCT2 or shared with other aggrephagy receptors was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis and signals governing the TRiC-to-monomer transition, the identity of the calcium channel modulated by CCT2 in immune cells, whether CCT2's oncogenic functions require the intact chaperonin or the monomeric form, and the full client repertoire in different tissue contexts.
  • Structural basis for monomer release from TRiC not determined
  • Calcium channel identity downstream of CCT2 in T cells unknown
  • Systematic TRiC-dependent vs. monomer-dependent substrate classification lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 8 GO:0038024 cargo receptor activity 4 GO:0140657 ATP-dependent activity 1
Localization
GO:0005576 extracellular region 3 GO:0005829 cytosol 3 GO:0005929 cilium 2
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-168256 Immune System 5 R-HSA-9612973 Autophagy 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3
Partners
ALDOACCDC181CCT3CCT5CTNNB1GLI1KRASTRIM21
Complex memberships
TRiC/CCT chaperonin complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 CCT2 functions as an aggrephagy receptor that binds aggregation-prone proteins independent of cargo ubiquitination and interacts with autophagosome marker ATG8s through a non-classical VLIR motif. Unlike ubiquitin-binding receptors (P62, NBR1, TAX1BP1), CCT2 specifically promotes autophagic degradation of solid protein aggregates with little liquidity. Accumulation of aggregation-prone proteins induces a functional switch of CCT2 from a chaperone subunit to an autophagy receptor by promoting CCT2 monomer formation, which exposes the VLIR motif for ATG8 interaction. Co-IP, pulldown, live-cell imaging, loss-of-function experiments in cells and mouse brain, domain mutagenesis (VLIR motif), fractionation assays distinguishing solid vs. liquid aggregates Cell High 35366418
2020 CCT2 enriched in UC-MSC-derived extracellular vesicles regulates calcium channels to affect Ca2+ influx and suppress CD154 (CD40L) synthesis in CD4+ T cells via the Ca2+-calcineurin-NFAT1 signaling pathway, thereby modulating inflammatory responses during liver ischemia/reperfusion injury. Protein mass spectrometry identification of CCT2 in EVs, in vivo liver IRI mouse model, mechanistic pathway analysis of Ca2+-calcineurin-NFAT1 signaling, flow cytometry for CD154 expression Advanced science Medium 32999825
2015 CCT2 (along with TCP1) is essential for survival of breast cancer cells; both genes encode subunits of the TRiC chaperonin complex and are recurrently amplified and overexpressed in breast cancer, with TCP1 expression regulated by PI3K signaling downstream of driver oncogene activation. RNAi-based functional genetic screen, copy number analysis, expression profiling, siRNA knockdown viability assays, PI3K pathway inhibition Experimental cell research Medium 25704758
2019 CCT2 (T-complex protein 1 subunit beta) interacts with Gli-1 under hypoxic conditions in colorectal cancer cells, facilitating Gli-1 folding and preventing its ubiquitination-mediated degradation by β-TrCP; reduction of CCT2 inhibits Gli-1-driven tumor induction. Mass spectrometry identification of CCT2-Gli-1 interaction, western blotting, immunofluorescence, RNAi knockdown, in vivo xenograft models Oncogene Medium 31462707
2016 Compound heterozygous mutations T400P and R516H in CCT2 (CCTβ) cause Leber congenital amaurosis (LCA) by destabilizing the chaperonin complex; mutant CCTβ proteins show reduced affinity for adjacent subunit CCTγ, impair proliferation in patient-derived iPSCs, fail to rescue knockdown phenotypes, and reduce the major client protein transducin β1 (Gβ1) in mouse retina where CCTβ and CCTγ are co-expressed in retinal ganglion cells and photoreceptor connecting cilia. Biochemical stability assays of mutant proteins, co-IP for CCTβ-CCTγ interaction, patient-derived iPSC proliferation assays, rescue experiments in 661W cells, Cct2 knockdown, immunostaining of mouse retina Scientific reports High 27645772
2018 Loss-of-function cct2 mutation (L394H-7del) in zebrafish causes small eye phenotype, attenuated retinal ganglion cell differentiation, disrupted retinal cell cycle, and increased neural retinal cell death; injection of wild-type human CCTβ RNA rescues the phenotype and restores Gβ1 protein levels, confirming CCT2's essential role in retinal development through cell cycle regulation. CRISPR-Cas9 mutagenesis, microscopy, immunostaining, TUNEL assay, EdU proliferation assay, RNA rescue injection Investigative ophthalmology & visual science High 29450543
2019 CCT2 and CCT5 are required for stabilization of Cdc20, which is necessary for MDRV p10.8-induced CDK4 degradation via the ubiquitin-proteasome pathway and subsequent cell cycle arrest and apoptosis; depletion of CCT2 reduced Cdc20 levels and reversed p10.8-mediated CDK4 degradation and apoptosis. siRNA depletion of CCT2/CCT5 and Cdc20, western blotting for CDK4/Cdc20 levels, apoptosis assays, cell cycle analysis Veterinary microbiology Medium 31282373
2023 The LCA-causative double mutation T400P/R516H in yeast CCT2 reduces the off-rate of ADP during ATP hydrolysis by CCT/TRiC, stabilizing the closed state of the chaperonin complex; this impedes CCT2 monomer exit from the complex required for its autophagy receptor function. ATPase activity of CCT/TRiC is stimulated by a non-folded substrate. Steady-state and transient kinetic analysis of ATPase activity in yeast CCT/TRiC carrying equivalent mutations, substrate-stimulated ATPase assays Communications biology High 37644231
2024 CCT2-mediated aggrephagy is regulated by two mechanisms in yeast (conserved in mammals): (1) Atg1 kinase phosphorylates Cct2 at Ser412 and Ser470, and disruption of these sites impairs solid aggrephagy by hindering Cct2-Atg8 binding; (2) Atg11 (selective autophagy adaptor) directly associates with Cct2 through its CC4 domain, and loss of this interaction weakens Cct2-Atg8 association. Phosphorylation site mutagenesis, in vivo phosphorylation assays, co-IP, domain mapping of Atg11-Cct2 interaction, aggrephagy functional assays, conservation validated in mammalian cells with LC3C EMBO reports High 39322741
2024 E3 ubiquitin ligase Trim21 facilitates CCT2 ubiquitination and proteasomal degradation in breast cancer cells, reversing CCT2's pro-tumorigenic effects. CCT2 promotes cancer progression via JAK2/STAT3 signaling activation. Exosomal CCT2 from breast cancer cells suppresses CD4+ T cell activation by constraining Ca2+-NFAT1 signaling and reducing CD40L (CD154) expression. Co-IP for Trim21-CCT2 interaction, ubiquitination assay, CCT2 knockdown/overexpression with JAK2/STAT3 pathway readouts, exosome isolation and treatment experiments, Ca2+-NFAT1 signaling analysis Cell death & disease Medium 39079960
2024 PRRSV nsp3 enhances the interaction between porcine MDA5 and CCT2, promoting aggregate formation and autophagic clearance of the MDA5-CCT2-nsp3 complex independently of ubiquitination, thereby suppressing innate immune signaling via CCT2's aggrephagy receptor function. Co-IP for MDA5-CCT2-nsp3 interaction, autophagy flux assays, MDA5 aggregate formation analysis, nsp3 overexpression, PRRSV infection model Virologica Sinica Medium 38272236
2024 CCT2 directly binds to KRAS protein (shown by co-IP, mass spectrometry, and surface plasmon resonance), leading to increased KRAS stability and upregulated downstream KRAS signaling in glioblastoma. Dihydroartemisinin directly binds CCT2 and decreases KRAS expression and signaling; CCT2 overexpression rescues the inhibitory effect of dihydroartemisinin. Co-immunoprecipitation, mass spectrometry, surface plasmon resonance (direct binding measurement), CCT2 overexpression rescue, glioblastoma animal model Cancer letters High 38582394
2024 LASV matrix protein (LASV-Z) interacts with CCT2 via glutamine-29 and tyrosine-48 residues, hindering actin and tubulin folding; cytoskeleton disruption caused by this interaction blocks lysosomal enzyme transit and autophagosome-lysosome fusion, promoting autophagosome accumulation that facilitates LASV-like particle budding. Mutation of the LASV-Z interaction sites reduces CCT2 binding and restores autophagic flux. Co-IP, site-directed mutagenesis of LASV-Z interaction residues, autophagy flux assays (LC3/LAMP1 co-localization), cytoskeleton disruption analysis, VLP budding assay Autophagy Medium 39007910
2024 CCT2 prevents β-catenin proteasomal degradation in epithelial ovarian cancer by recruiting the HSP105-PP2A dephosphorylation complex to β-catenin via direct physical interaction, preventing phosphorylation-induced proteasomal degradation and causing intracellular accumulation of active β-catenin with increased Wnt signaling. Co-IP for CCT2-β-catenin and CCT2-HSP105-PP2A interactions, ubiquitination assay, CCT2 KD/OE with Wnt pathway readouts, cancer stem cell functional assays Molecular biology reports Medium 38165547
2024 CCT2 is identified as a critical mediator of acquired resistance to third-generation EGFR-TKIs in lung cancer; mechanistically, CCT2 recruits TRIM28 to catalyze SUMO2 modification of TMX1, inhibiting its ubiquitination and enhancing TMX1 protein stability, which promotes TMX1-dependent ROS clearance conferring drug resistance. CRISPR/Cas9 genome-wide screen, TMT proteomics, co-IP for CCT2-TRIM28-TMX1 complex, SUMO2 modification assay, ubiquitination assay, ROS measurement, xenograft models Cell death and differentiation Medium 41168408
2024 CCT2 knockdown reduces STAT3 phosphorylation and impairs HCC cell proliferation, migration, invasion, and stemness in vitro and in vivo; IL-6 treatment rescues phosphorylated STAT3 levels and counteracts CCT2 knockdown effects, placing CCT2 upstream of STAT3 activation in hepatocellular carcinoma. siRNA knockdown, EdU/colony formation/Transwell assays, flow cytometry, xenograft and hematogenous metastasis models, western blotting for p-STAT3, IL-6 rescue experiment Oncology reports Medium 41789667
2024 Compound heterozygous Cct2 mutations (T400P/R516H) in mice cause aberrant cone cell lamination and early lethality; R516H homozygosity causes photoreceptor degeneration with significant depletion of TRiC/CCT substrate proteins in retina. CCDC181 is identified as a CCTβ-interacting protein whose localization to photoreceptor connecting cilia is compromised in mutant mice. Generation of knock-in mouse models, histology, immunostaining, retinal phenotyping, co-IP for CCTβ-CCDC181 interaction, localization analysis of ciliary proteins Communications biology High 38830954
2026 CCT2 directly interacts with and stabilizes the glycolytic enzyme ALDOA, as shown by co-immunoprecipitation and GST pulldown, increasing extracellular acidification rate, glucose uptake, and lactate production in HCC cells. CCT2 also promotes M2 macrophage polarization through exosome-mediated mechanisms, creating an immunosuppressive tumor microenvironment; CCT2 knockdown enhances anti-tumor efficacy of PD-1 blockade in mouse models. Co-immunoprecipitation, GST pulldown assay, extracellular acidification rate measurement, glucose uptake assay, lactate quantification, metabolomics, THP1 co-culture assay, exosome treatment, in vivo xenograft with PD-1 blockade International journal of biological sciences Medium 42003909
2026 Site-specific photo-cross-linking coupled with quantitative proteomics identified CCT2 as a cGAS-associated factor; CCT2 attenuates cGAS-STING innate immune signaling by facilitating autophagy-mediated turnover of DNA-bound cGAS aggregates, limiting persistence of immunostimulatory cytosolic DNA signals. Residue-resolved photo-cross-linking, quantitative proteomics, cGAS-STING signaling assays, autophagy flux analysis, CCT2 loss-of-function ACS chemical biology Medium 42043443
2025 Histone H3K18 lactylation upregulates METTL3 expression, which enhances CCT2 translation through m6A modification of CCT2 mRNA; elevated CCT2 in turn weakens CD8+ T cell activity by inhibiting Ca2+ influx, thereby mediating immune evasion in gastric cancer. CHIP for H3K18la at METTL3 locus, RIP assay for METTL3-CCT2 mRNA m6A modification, CCT2 overexpression/knockdown, Ca2+ influx measurement, T cell cytotoxicity assay, flow cytometry, homograft mouse model Cellular and molecular life sciences Medium 41288742
2024 CCT2 knockdown in primary cilia studies revealed that the TRiC/CCT chaperonin complex (including CCT2 and CCT3) forms a co-complex with BBS chaperonin-like proteins required for the localization of adhesion GPCR ADGRV1 to primary cilia; in the absence of this co-complex, ADGRV1 is depleted from the base of primary cilia and degraded via the proteasome. siRNA knockdown of CCT2/CCT3/BBS6, ciliogenesis phenotyping (ciliated cell count, cilia length), immunofluorescence localization of ADGRV1, proteasome inhibitor rescue bioRxivpreprint Low bio_10.1101_2024.10.31.621306

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2008 Many sequence variants affecting diversity of adult human height. Nature genetics 520 18391951
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2012 Role of TAZ as mediator of Wnt signaling. Cell 407 23245942
2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 386 15324660
2005 Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proceedings of the National Academy of Sciences of the United States of America 383 16009940
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2022 CCT2 is an aggrephagy receptor for clearance of solid protein aggregates. Cell 144 35366418
2020 Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 103 32999825
2015 Two members of the TRiC chaperonin complex, CCT2 and TCP1 are essential for survival of breast cancer cells and are linked to driving oncogenes. Experimental cell research 85 25704758
2019 Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer. Oncogene 38 31462707
2016 CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability. Scientific reports 37 27645772
2013 Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma. World journal of surgical oncology 31 23782473
2019 Cdc20 and molecular chaperone CCT2 and CCT5 are required for the Muscovy duck reovirus p10.8-induced cell cycle arrest and apoptosis. Veterinary microbiology 29 31282373
2018 Mutation in the Zebrafish cct2 Gene Leads to Abnormalities of Cell Cycle and Cell Death in the Retina: A Model of CCT2-Related Leber Congenital Amaurosis. Investigative ophthalmology & visual science 23 29450543
2024 Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4+T cell activation in breast cancer. Cell death & disease 21 39079960
2024 PRRSV degrades MDA5 via dual autophagy receptors P62 and CCT2 to evade antiviral innate immunity. Virologica Sinica 20 38272236
2022 TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway. Translational oncology 20 35429902
2022 CCT2, a newly identified aggrephagy receptor in mammals, specifically mediates the autophagic clearance of solid protein aggregates. Autophagy 17 35699934
2023 Circ-CCT2 Activates Wnt/β-catenin Signaling to Facilitate Hepatoblastoma Development by Stabilizing PTBP1 mRNA. Cellular and molecular gastroenterology and hepatology 12 37866478
2023 Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer's disease. Frontiers in genetics 9 36704351
2024 Targeting the molecular chaperone CCT2 inhibits GBM progression by influencing KRAS stability. Cancer letters 7 38582394
2023 Reduced ADP off-rate by the yeast CCT2 double mutation T394P/R510H which causes Leber congenital amaurosis in humans. Communications biology 6 37644231
2024 CCT2 prevented β-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer. Molecular biology reports 5 38165547
2024 Lassa virus Z protein hijacks the autophagy machinery for efficient transportation by interrupting CCT2-mediated cytoskeleton network formation. Autophagy 5 39007910
2023 Tat-CCT2 Protects the Neurons from Ischemic Damage by Reducing Oxidative Stress and Activating Autophagic Removal of Damaged Protein in the Gerbil Hippocampus. Neurochemical research 5 37561257
2024 The essential role of CCT2 in the regulation of aggrephagy. Frontiers in aging neuroscience 4 39478698
2024 Compound heterozygous mutations in a mouse model of Leber congenital amaurosis reveal the role of CCT2 in photoreceptor maintenance. Communications biology 3 38830954
2024 Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy. EMBO reports 3 39322741
2024 CCT2 Regulates ZEB1-Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma. Discovery medicine 2 39327245
2024 Neuroprotective Effects of Chaperonin Containing TCP1 Subunit 2 (CCT2) on Motor Neurons Following Oxidative or Ischemic Stress. Neurochemical research 2 39614031
2026 Knockdown of CCT2 inhibits the malignant progression of hepatocellular carcinoma cells by impairing STAT3 activation. Oncology reports 0 41789667
2026 CCT2 Orchestrates Glycolysis and Exosome-Mediated M2 Macrophage Polarization in HCC tumorigenesis. International journal of biological sciences 0 42003909
2026 Site-Specific Photo-Cross-Linking Reveals CCT2 as a Regulator of cGAS-STING Signaling via Clearance of cGAS-DNA Condensates. ACS chemical biology 0 42043443
2025 Clinical characterization of CCT2 and its role in autophagy regulation during age-related macular degeneration. Scientific reports 0 40374738
2025 CRISPR/Cas9 library screening uncovered CCT2 as a critical driver of acquired resistance to EGFR-targeted therapy by stabilizing TMX1 in non-small cell lung cancer. Cell death and differentiation 0 41168408
2025 IGFBP7 and CCT2 are novel lactylation-driven mediators of endothelial-to-mesenchymal transition in idiopathic pulmonary fibrosis. Functional & integrative genomics 0 41261179
2025 Histone lactylation drives METTL3 upregulation-mediated RNA m6A modification of CCT2 to hinder CD8+ T cell survival in gastric cancer. Cellular and molecular life sciences : CMLS 0 41288742