Affinage

TCP1

T-complex protein 1 subunit alpha · UniProt P17987

Round 2 corrected
Length
556 aa
Mass
60.3 kDa
Annotated
2026-04-28
130 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TCP1 is the founding subunit of the hetero-oligomeric cytosolic chaperonin TRiC/CCT, an essential ATP-dependent molecular chaperone that folds obligate substrates—most notably tubulin and actin—through sequential nucleotide-driven conformational rearrangements of its double-ring architecture (PMID:1630491, PMID:1361170, PMID:17417821). Genetic loss of TCP1 or related CCT subunits in yeast is lethal, causing defective microtubule and actin assembly, aberrant chromosome segregation, and spindle malformation, and in mammalian cells TCP1 localizes to centrosomes where it is required for microtubule nucleation (PMID:1901944, PMID:7916460, PMID:8557692). Beyond cytoskeletal clients, TRiC/CCT folds HDAC3 to enable SMRT corepressor complex assembly, and its activity is regulated by RSK/S6K phosphorylation of CCT-β at Ser-260 downstream of Ras-MAPK and PI3K-mTOR signaling, as well as by cofactors including Hop/p60 and caveolin-1 (PMID:12502735, PMID:19332537, PMID:9792653, PMID:16568240). TCP1 overexpression stabilizes oncoproteins such as c-Myc (by reducing its ubiquitination via AKT/GSK-3β and ERK pathways) and activates AKT/mTOR signaling to suppress autophagy and apoptosis, establishing a pro-tumorigenic role in hepatocellular carcinoma and acute myeloid leukemia (PMID:40185866, PMID:34750375).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 Medium

    Before its chaperonin function was recognized, TCP1 was localized to the trans-Golgi network and spermatid acrosome, initially suggesting a role in exocytic transport — this placed TCP1 on the subcellular map but left its molecular activity unknown.

    Evidence Immunofluorescence and subcellular fractionation in tissue culture cells and spermatids

    PMID:2655925

    Open questions at the time
    • Golgi localization was not confirmed by immuno-EM or functional transport assays
    • Relationship to later-identified cytosolic chaperonin function unclear
  2. 1991 High

    Genetic analysis in yeast established that TCP1 is an essential gene required for microtubule-mediated processes, answering whether TCP1 has an indispensable cellular function.

    Evidence Temperature-sensitive tcp1 yeast mutants causing growth arrest, abnormal tubulin structures, and antimitotic drug sensitivity

    PMID:1901944

    Open questions at the time
    • Biochemical mechanism of TCP1 action on tubulin was not yet established
    • Whether TCP1 acts alone or in a complex was unknown
  3. 1992 High

    Biochemical reconstitution revealed that TCP1 resides in a ~900–970 kDa hetero-oligomeric ring complex (TRiC/CCT) that binds unfolded polypeptides and releases them in a folded, assembly-competent state through ATP hydrolysis, establishing the eukaryotic cytosolic chaperonin paradigm.

    Evidence Reticulocyte lysate translation/sucrose gradient fractionation, purified TRiC renaturation of luciferase and tubulin, electron microscopy

    PMID:1361170 PMID:1630491

    Open questions at the time
    • Subunit arrangement and stoichiometry within the ring were unknown
    • Whether individual subunits have distinct substrate contacts was not addressed
  4. 1994 High

    Yeast genetics extended the TRiC client repertoire to actin and demonstrated that all CCT subunits participate in a single essential process, resolving whether the complex serves multiple cytoskeletal substrates or only tubulin.

    Evidence Synthetic lethality among CCT subunit mutations, allele-specific interactions with act1 and tub mutants, dosage suppression of actin defects

    PMID:7865875 PMID:7908441 PMID:7916460

    Open questions at the time
    • Direct biochemical demonstration of actin folding by purified CCT was still lacking at this point
    • Non-cytoskeletal substrates were not yet identified
  5. 1996 High

    TCP1 was shown to localize within centrosomes and to be functionally required for centrosomal microtubule nucleation, answering whether the chaperonin has a specific spatial role beyond bulk cytosolic folding.

    Evidence Immunofluorescence of centrosomes and anti-TCP1 antibody microinjection blocking microtubule regrowth after nocodazole washout

    PMID:8557692

    Open questions at the time
    • Whether TCP1 folds γ-tubulin or other centrosomal clients was not determined
    • Mechanism of TCP1 enrichment at centrosomes unknown
  6. 1997 High

    Biophysical studies established the conformational cycle of CCT: nucleotide binding switches the ring between high- and low-affinity substrate-binding states, and each subunit occupies a fixed position within the ring, resolving how allosteric communication drives the folding cycle.

    Evidence Micro-complex mapping of subunit neighbors, electron microscopy, intrinsic fluorescence, sedimentation velocity, and nucleotide exchange assays on purified CCT

    PMID:9153422 PMID:9250675

    Open questions at the time
    • Atomic-resolution structure of the complete folding cycle was not yet available
    • Order of ATP hydrolysis around the ring not determined
  7. 1998 High

    Identification of Hop/p60 as a nucleotide-dependent negative regulator of CCT folding activity revealed the first co-chaperone modulating TRiC function, and a disassembly/reassembly cycle showed the complex itself is dynamically remodeled.

    Evidence Co-IP of Hop/p60 with purified CCT, luciferase reactivation inhibition, nucleotide exchange stimulation; reticulocyte lysate subunit incorporation assays

    PMID:9563827 PMID:9792653

    Open questions at the time
    • Physiological contexts regulating Hop/CCT interaction in vivo were unexplored
    • Whether disassembly/reassembly occurs in intact cells was not shown
  8. 2002 High

    Discovery that TRiC folds HDAC3 and primes it for SMRT corepressor binding expanded the client repertoire beyond cytoskeletal proteins to transcriptional regulators, establishing TRiC as a general folding machine for complex protein topologies.

    Evidence Co-IP of HDAC3 with TRiC, ATP-dependent folding assays, dominant-negative CCT expression, HDAC enzymatic activity readout

    PMID:12502735

    Open questions at the time
    • Scope of non-cytoskeletal TRiC clients was not yet systematically defined
    • Structural basis for HDAC3 recognition by TRiC unknown
  9. 2007 High

    FRET measurements on doubly-labeled actin demonstrated that TRiC actively stretches and rearranges bound substrate upon ATP binding, resolving the long-standing question of whether chaperonins passively sequester or actively remodel client conformations.

    Evidence FRET on four distinct doubly-fluorescein-labeled actin variants bound to purified TRiC ± ATP

    PMID:17417821

    Open questions at the time
    • Cryo-EM snapshots of actin at each step of the rearrangement cycle were not available
    • Whether all substrates undergo the same stretching mechanism was untested
  10. 2009 High

    Convergent phosphorylation of CCT-β Ser-260 by RSK (via Ras-MAPK) and S6K (via PI3K-mTOR) revealed that growth factor signaling directly regulates chaperonin activity, answering how extracellular signals modulate protein folding capacity.

    Evidence Mass spectrometry site identification, mutagenesis (S260A), MEK/RSK inhibitors, RNAi rescue of proliferation defect

    PMID:19332537

    Open questions at the time
    • How Ser-260 phosphorylation alters CCT conformation or ATPase kinetics was not determined
    • Whether other CCT subunits are similarly regulated was unknown
  11. 2010 High

    In vivo perturbation of CCT in mouse photoreceptors caused rapid retinal degeneration and loss of ~200 proteins, demonstrating tissue-specific dependence on CCT folding capacity for sensory neuron survival.

    Evidence Transgenic dominant-negative phosducin-like protein expression in mouse rods, quantitative proteomics, histology

    PMID:20852191

    Open questions at the time
    • Which of the ~200 affected proteins are direct CCT clients versus secondary losses was not resolved
    • Human retinal disease association not established
  12. 2015 High

    Misato was identified as a stoichiometric CCT cofactor required for complex stability, and TCP1 expression was found to be PI3K-regulated in breast cancer, linking chaperonin biogenesis to oncogenic signaling.

    Evidence AP-MS of Misato, RNAi phenocopy in Drosophila, tubulin polymerization assay; TCP1 copy number/expression analysis and PI3K inhibition in breast cancer lines

    PMID:25704758 PMID:26096973

    Open questions at the time
    • Whether Misato regulation occurs in mammalian cells was not shown
    • Whether TCP1 amplification is a driver or passenger event in breast cancer was unresolved
  13. 2021 Medium

    TCP1 was shown to interact with AKT and mTOR to activate AKT/mTOR signaling, suppress autophagy, and promote drug resistance in AML, and CCT was found to preferentially retain mutant smooth-muscle α-actin (ACTA2 R149C), modulating disease penetrance — both discoveries expanded the functional scope from folding to signaling regulation and quality control of disease-relevant variants.

    Evidence Co-IP of TCP1 with AKT/mTOR, xenograft models, pharmacological rescue in AML cells; CRISPR knock-in Acta2R149C mice, TIRF microscopy, co-IP of mutant actin with CCT

    PMID:34600884 PMID:34750375

    Open questions at the time
    • Whether TCP1 activates AKT via direct folding or scaffolding is unresolved
    • Generalizability of mutant-actin retention mechanism to other actin disease variants untested
    • AKT/mTOR interaction not independently replicated
  14. 2025 Medium

    TCP1 was shown to stabilize c-Myc protein by reducing its ubiquitination through AKT/GSK-3β and ERK pathways, and TCP1 knock-in mice developed hepatocellular carcinoma more readily, providing the first direct in vivo genetic evidence for an oncogenic role of TCP1 itself.

    Evidence Co-IP of TCP1 with c-Myc, ubiquitination assays, TCP1 knock-in mouse DEN-HCC model

    PMID:40185866

    Open questions at the time
    • Whether TCP1 directly folds c-Myc or acts as a scaffolding adaptor is not distinguished
    • Contribution of other CCT subunits versus TCP1 alone not delineated
    • Single-lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of TRiC bound to diverse clients at each step of the folding cycle, the full scope of the obligate client proteome in different tissues, and whether the emerging non-folding roles of TCP1 (signaling scaffold, oncoprotein stabilizer) are chaperonin-complex-dependent or involve monomeric/sub-complex TCP1 species.
  • Complete client proteome uncharacterized in most tissues
  • Monomeric versus complex-associated TCP1 functions not distinguished
  • No therapeutic modulator of CCT activity has reached clinical testing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 5 GO:0140657 ATP-dependent activity 4
Localization
GO:0005829 cytosol 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4
Partners
AKT1CAV1CCT2HDAC3MSTMTORMYCSTIP1
Complex memberships
TRiC/CCT

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 TCP1 is the major constituent of a 900 kDa cytosolic complex that binds newly translated tubulin subunits in a protease-sensitive (non-native) conformation; addition of Mg-ATP (but not non-hydrolysable analogues) releases assembly-competent, protease-resistant tubulin, establishing TCP1 as an ATP-dependent molecular chaperone required for tubulin biogenesis. Rabbit reticulocyte lysate translation, sucrose gradient fractionation, ATP hydrolysis assays, protease sensitivity assay, immunoprecipitation with anti-TCP1 monoclonal antibody Nature High 1630491
1992 TCP-1 is part of a hetero-oligomeric ~970 kDa ring complex (TRiC) containing several structurally related subunits of 52–65 kDa; TRiC binds unfolded polypeptides, prevents their aggregation, and mediates ATP-dependent renaturation of firefly luciferase and tubulin in vitro, functioning independently of a GroES co-chaperonin. Purification of TRiC complex, electron microscopy, in vitro renaturation assays with luciferase and tubulin, ATP hydrolysis assays The EMBO journal High 1361170
1991 The yeast homolog of TCP1 is an essential gene; temperature-sensitive tcp1-1 mutation causes growth arrest with accumulation of multinucleate and anucleate cells, morphologically abnormal tubulin structures, and hypersensitivity to antimitotic compounds, demonstrating TCP1 affects microtubule-mediated processes in vivo. Yeast genetic analysis, conditional lethal mutation, immunofluorescence with anti-tubulin antibodies, antimitotic drug sensitivity assay Molecular and cellular biology High 1901944
1994 Two yeast TCP-1-related proteins (Bin2p and Bin3p, CCT subunits) are required for microtubule and actin assembly in vivo; mutations cause aberrant chromosome segregation and actin defects; all double-mutant combinations among TCP1-family members are inviable, indicating they act in a common essential process. Yeast genetics, cold-sensitive mutations, in vivo fluorescence microscopy of actin and microtubules, synthetic lethality analysis, benomyl hypersensitivity Proceedings of the National Academy of Sciences of the United States of America High 7916460
1994 Yeast TCP1 protein affects both actin and microtubule function; tcp1 alleles show allele-specific genetic interactions with tub1-1, tub2-402, act1-1, and act1-4 mutations but not other cytoskeletal mutants; overproduction of wild-type Tcp1p partially suppresses act1-1 and act1-4 growth defects; Tcp1p localizes to the cytoplasm and cell cortex. Yeast double-mutant analysis, genetic suppression, immunofluorescence microscopy of actin and tubulin, cell fractionation/localization Molecular biology of the cell High 7865875
1989 TCP-1 protein is associated with the cytoplasmic aspect of Golgi membranes (trans-Golgi network) in tissue culture cells by indirect immunofluorescence; in spermatids it localizes to structures associated with the developing acrosome, suggesting a role in exocytic protein transport. Rat monoclonal antibody immunoprecipitation, Western blotting, indirect immunofluorescence microscopy, subcellular fractionation Cell Medium 2655925
1996 TCP-1 localizes within the centrosome in interphase and mitotic cells; microinjection of anti-TCP-1 antibodies blocks microtubule regrowth from centrosomes after nocodazole treatment, demonstrating TCP-1 is required for centrosomal microtubule nucleation. Indirect immunofluorescence, centrosome enrichment, antibody microinjection into living cells, microtubule regrowth assay The Journal of biological chemistry High 8557692
1994 TCP1 beta (a second essential CCT subunit) shares 35% sequence identity with TCP1 alpha; its gene is essential in yeast; temperature-sensitive mutations arrest cells as large-budded cells with replicated DNA in single nuclear masses and abnormal tubulin staining, supporting a role in mitotic spindle formation; TCP1 alpha cannot functionally replace TCP1 beta. Gene disruption, temperature-sensitive mutations, flow cytometry, immunofluorescence with anti-tubulin antibodies, yeast genetics Proceedings of the National Academy of Sciences of the United States of America High 7908441
1997 CCT micro-complexes composed of subsets of CCT subunits reveal that each subunit associates with only one or two specific partner subunits, implying a unique fixed topology within the toroidal ring; this narrows the subunit arrangement from 5040 combinatorial possibilities to a single probable orientation. Biochemical characterization of CCT micro-complexes, immunoprecipitation, gel filtration, Western blotting with subunit-specific antibodies The EMBO journal High 9250675
1997 CCT can simultaneously bind two substrate protein chains in its cavity; conformational changes distinguishable by electron microscopy and intrinsic fluorescence occur upon ATP or ADP binding and upon substrate binding; nucleotide exchange regulates the affinity of CCT for unfolded substrates, switching between high- and low-affinity conformations. Radiolabeled substrate binding, electron microscopy, sedimentation velocity, intrinsic fluorescence measurements, nucleotide exchange assays Biochemistry High 9153422
1998 The chaperone cofactor Hop/p60 directly interacts with CCT in an ATP/ADP-dependent manner through its C-terminal sequences; Hop/p60 stimulates nucleotide exchange on CCT, decreases substrate binding to CCT, and inhibits CCT-mediated luciferase reactivation in combination with hsc70/hsp40, identifying Hop/p60 as a negative regulator of CCT folding activity. Co-immunoprecipitation with purified CCT and Hop/p60, luciferase reactivation assays, nucleotide exchange assays The Journal of biological chemistry High 9792653
1998 CCT undergoes a nucleotide-dependent disassembly to single rings and reassembly cycle; newly translated CCT subunits incorporate into the endogenous CCT complex via this single-ring intermediate mechanism, demonstrating the complex can remodel itself through an ATP-dependent pathway. In vitro translation of CCT subunit mRNAs in reticulocyte lysate, sucrose gradient fractionation, incorporation assays Biological chemistry Medium 9563827
2002 TRiC/CCT is required for proper folding of HDAC3 in an ATP-dependent process; TRiC primes HDAC3 for interaction with the corepressor SMRT, which then displaces TRiC from HDAC3 to yield active histone deacetylase; this places TRiC as an obligate chaperone upstream of SMRT-HDAC3 repression complex assembly. Co-immunoprecipitation, ATP dependence assays, HDAC enzyme activity assays, dominant-negative CCT subunit expression Genes & development High 12502735
2009 CCT is a physiological substrate for RSK (p90 ribosomal S6 kinase) and S6K (p70 ribosomal S6 kinase); RSK phosphorylates the CCT-beta subunit at Ser-260 in response to growth factors activating the Ras-MAPK pathway; insulin utilizes S6K to phosphorylate the same site via the PI3K-mTOR pathway; phosphorylation-deficient S260A mutant CCT-beta fails to rescue proliferation defects caused by CCT-beta knockdown. Mass spectrometry identification of phosphorylation site, site-directed mutagenesis, MEK and RSK inhibitors, RNA interference, cell proliferation rescue assay The Journal of biological chemistry High 19332537
2009 The intracellular beta-tubulin/CCT-beta complex is constitutively formed; the small molecule N-iodoacetyl-tryptophan (I-Trp) alkylates Cys354 in beta-tubulin at the binding interface with CCT-beta, disrupting the complex and inducing apoptosis; Cys354 mutation abolishes I-Trp incorporation; higher CCT-beta levels in drug-resistant cells correlate with greater susceptibility to I-Trp. Proteomic analysis, protein fingerprinting, site-directed mutagenesis, co-immunoprecipitation, apoptosis assays, CCT-beta siRNA knockdown Cancer research High 19690144
2010 Reduced binding of glucocerebrosidase (GCase) to the TRiC/CCT complex in Gaucher disease cells correlates with defective maturation of nascent GCase; increased interaction between GCase and the E3 ubiquitin ligase c-Cbl leads to proteasomal degradation of GCase, suggesting TRiC normally facilitates correct GCase folding and protects it from ubiquitin-mediated degradation. Co-immunoprecipitation of GCase with TRiC and c-Cbl, proteasome inhibitor (lactacystin) experiments, patient-derived fibroblasts Proceedings of the National Academy of Sciences of the United States of America Medium 21098288
2010 CCT disruption in mouse photoreceptors via transgenic dominant-negative mutant of the CCT cofactor phosducin-like protein causes malformation of rod outer segments and rapid retinal degeneration; quantitative proteomics identified ~200 proteins significantly affected, including peripherin-2, Rom1, rhodopsin, transducin, and PDE6, demonstrating CCT is required for morphogenesis and survival of retinal sensory neurons. Transgenic mouse model, dominant-negative cofactor expression, quantitative proteomics, histology Molecular & cellular proteomics High 20852191
2011 The CCT/TRiC complex is present on the surface of capacitated spermatozoa and forms a multimeric receptor complex with zona pellucida-binding protein 2 (ZP-binding protein 2) that mediates sperm binding to the zona pellucida of the oocyte, as demonstrated by blue native PAGE, far Western blotting, and proximity ligation assay. Blue native PAGE, far Western blotting, proximity ligation assay, capacitation assays The Journal of biological chemistry Medium 21880732
2012 CCT subunit eta (CCTη) regulates NF-κB transcriptional activity downstream of IKK; CCTη knockdown alters p65 acetylation at lysines 122 and 123, presumably by modulating CBP histone acetyltransferase activity, impairing termination of NF-κB-dependent transcription of CCL5/RANTES and CXCL10/IP10. RNAi screening in Drosophila and mammalian cells, reporter gene assays, ChIP, p65 acetylation analysis by mutation of K122/K123 PloS one Medium 22860050
2014 TCP1 complex proteins interact with phosphorothioate antisense oligonucleotides (PS-ASOs) and enhance their antisense activity; TCP1-beta subunit co-localizes with PS-ASOs in nuclear PS-bodies; upon RAN depletion, cytoplasmic PS-body-like structures appear and nuclear PS-ASO concentrations decrease, suggesting TCP1 facilitates nuclear import of PS-ASOs via the RAN-mediated pathway. Cell transfection, co-immunoprecipitation, co-localization (fluorescence microscopy), RAN knockdown, antisense activity assays Nucleic acids research Medium 24861627
2014 The CCT complex directly binds to the cytoplasmic domain of LOX-1 (lectin-like oxidized LDL receptor); 6 of 8 CCT subunits were identified by affinity isolation; the CCT-LOX-1 interaction is direct, ATP-dependent, and suppressed by OxLDL treatment, as confirmed by co-immunoprecipitation and immunostaining in human umbilical vein endothelial cells. Affinity isolation, mass spectrometry, co-immunoprecipitation, immunostaining, ATP dependence assays FEBS letters Medium 24846140
2006 Caveolin-1 interacts with TCP-1 via its first 32 N-terminal amino acids; caveolin-1 expression is required for CCT actin-folding activity induction in response to insulin; phosphorylation of caveolin-1 at Tyr14 causes its dissociation from TCP-1 and activates actin folding; the mechanism involves the cytoskeleton linker filamin, which is a negative regulator of this pathway. Co-immunoprecipitation, actin folding assays, site-directed mutagenesis (Tyr14), insulin stimulation, filamin interaction analysis Cellular and molecular life sciences Medium 16568240
2007 TRiC actively rearranges bound actin: FRET measurements on doubly fluorescein-labeled actin variants show that actin is stretched upon initial TRiC binding and further rearranged upon ATP binding, demonstrating an active (not passive) chaperonin mechanism that is evolutionarily conserved from bacteria (GroEL) to eukaryotes. FRET measurements using four distinct doubly-labeled actin variants, ATP binding/hydrolysis assays with purified TRiC Biochemistry High 17417821
2015 Misato (Mst) associates stoichiometrically with the TCP-1 complex and Tubulin Prefoldin complex; RNAi depletion of any TCP-1 subunit in Drosophila phenocopies mst mutations causing monopolar/disorganized spindles; Mst is required for TCP-1 complex stability; tubulin polymerization efficiency and stability are drastically reduced in mst mutants, identifying Mst as a co-factor stabilizing the TCP-1 complex during tubulin folding. Affinity purification mass spectrometry (AP-MS), in vivo RNAi depletion, spindle assembly assays, tubulin polymerization assays, structural bioinformatics Current biology High 26096973
2015 TCP1 and CCT2 subunits are recurrently amplified and overexpressed in breast cancer; TCP1 expression is regulated by PI3K signaling downstream of driver oncogene activation; RNAi-mediated depletion of TCP1 or CCT2 impairs breast cancer cell growth/survival in vitro, establishing TRiC subunits as functionally required for cancer cell proliferation. RNAi knockdown, copy number analysis, expression analysis, PI3K pathway inhibition, cell viability assays Experimental cell research Medium 25704758
2018 CCT folds actin through a sequential allosteric mechanism: non-native actin interacts with specific CCT subunits and is annealed through sequential ATP binding and hydrolysis around and across the double-ring; CCT releases a folded but 'soft' ATP-G-actin monomer that is energetically trapped ~80 kJ/mol uphill on the folding energy surface by its ATP-Mg2+/Ca2+ clasp, with this energy being re-explored in F-actin. Review and synthesis of structural, biochemical, and biophysical data including cryo-EM, free-energy modeling, and ATP hydrolysis studies The Biochemical journal Medium 30291170
2021 TCP1 interacts with AKT and mTOR to activate AKT/mTOR signaling, suppressing autophagy and adriamycin-induced apoptosis in AML cells; TCP1 overexpression increases drug resistance; pharmacological inhibition of AKT/mTOR restores autophagy and sensitizes TCP1-overexpressing cells to adriamycin, placing TCP1 upstream of AKT/mTOR in this pathway. Co-immunoprecipitation of TCP1 with AKT and mTOR, RNA interference, TCP1 overexpression, pharmacological AKT/mTOR inhibition, apoptosis and autophagy assays, xenograft models Cell death & disease Medium 34750375
2021 The ACTA2 R149C mutant smooth muscle α-actin is retained in the chaperonin-containing TCP-1 (CCT) folding complex more than wild-type actin; this enhanced CCT retention reduces mutant SM α-actin levels in smooth muscle cells, which minimizes the functional impact of the mutation and may account for reduced penetrance of aortic disease in Acta2R149C/+ mice. CRISPR/Cas9 knock-in mouse model, co-immunoprecipitation of actin with CCT, total internal reflection fluorescence microscopy, in vitro motility assays The Journal of biological chemistry High 34600884
2025 TCP1 stabilizes c-Myc protein through the AKT/GSK-3β and ERK signaling pathways; co-immunoprecipitation shows TCP1 directly interacts with c-Myc; ubiquitination assays demonstrate TCP1 reduces c-Myc ubiquitination and proteasomal degradation; TCP1 knock-in mice develop DEN-induced hepatocellular carcinoma more readily, establishing an oncogenic role. Co-immunoprecipitation, ubiquitination assays, TCP1 knock-in mouse model, DEN-induced HCC model, TCP1 knockdown in vitro and in vivo Communications biology Medium 40185866
2016 CCT (chaperonin containing TCP-1) is the intracellular target of the cytotoxic peptide CT20p; overexpression of CCT-beta (CCTβ) enhances susceptibility to CT20p; CT20p treatment reduces tubulin levels and inhibits cell migration, consistent with CCT being required for tubulin folding and cytoskeletal integrity in cancer cells. Protein pull-down with mass spectrometry, CCTβ overexpression, cytotoxicity assays, migration assays, tubulin quantification Clinical cancer research Medium 27012814
2020 CCT-beta (CCTβ) directly binds and stabilizes XIAP and β-catenin (shown by co-immunoprecipitation); CCTβ knockdown decreases XIAP levels, reduces AKT Ser473 phosphorylation, reduces GSK3β phosphorylation, and decreases nuclear β-catenin, reducing chemoresistance and migration; CCTβ overexpression restores these effects, placing CCT in the AKT-GSK3β-β-catenin and XIAP-Survivin pathways. Co-immunoprecipitation, CCTβ knockdown and overexpression, Western blotting for pathway components, chemoresistance and migration/invasion assays Cancers Medium 33371405
2024 METTL14 mediates m6A methylation of TCP1 mRNA, stabilizing the transcript and upregulating TCP1 protein in AML cells; elevated TCP1 promotes proliferation, migration, and inhibits apoptosis; TCP1 interacts with PPP2R2C (a PP2A regulatory subunit) as a functional target mediating malignant progression. Bioinformatics prediction, m6A methylation analysis, co-immunoprecipitation, Western blot, in vitro and in vivo functional assays Cellular signalling Medium 39033992

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
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
2006 Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Molecular cell 1260 16916647
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
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
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
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 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
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
2014 Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America 436 24927568
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
1992 TCP1 complex is a molecular chaperone in tubulin biogenesis. Nature 407 1630491
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
1992 Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits. The EMBO journal 374 1361170
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1995 The chaperonin containing t-complex polypeptide 1 (TCP-1). Multisubunit machinery assisting in protein folding and assembly in the eukaryotic cytosol. European journal of biochemistry 252 7601114
1995 Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells. Molecular microbiology 230 7752884
1997 Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from the subunit composition of CCT micro-complexes. The EMBO journal 162 9250675
2010 TCP1 modulates brassinosteroid biosynthesis by regulating the expression of the key biosynthetic gene DWARF4 in Arabidopsis thaliana. The Plant cell 152 20435901
1991 The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. Molecular and cellular biology 139 1901944
1994 Two yeast genes with similarity to TCP-1 are required for microtubule and actin function in vivo. Proceedings of the National Academy of Sciences of the United States of America 131 7916460
2008 Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation. Cell stress & chaperones 130 18595008
2002 Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex. Genes & development 118 12502735
1993 Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 101 8098536
1997 Cytoplasmic chaperonin containing TCP-1: structural and functional characterization. Biochemistry 98 9153422
1994 The essential yeast Tcp1 protein affects actin and microtubules. Molecular biology of the cell 95 7865875
1990 Sequence and structural homology between a mouse T-complex protein TCP-1 and the 'chaperonin' family of bacterial (GroEL, 60-65 kDa heat shock antigen) and eukaryotic proteins. Biochemistry international 94 1972327
2011 The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction. The Journal of biological chemistry 93 21880732
2007 Characterization of a tightly controlled promoter of the halophilic archaeon Haloferax volcanii and its use in the analysis of the essential cct1 gene. Molecular microbiology 87 17973910
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
1989 The t complex polypeptide 1 (TCP-1) is associated with the cytoplasmic aspect of Golgi membranes. Cell 85 2655925
2014 TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells. Nucleic acids research 84 24861627
2009 p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling. The Journal of biological chemistry 78 19332537
1996 Molecular chaperones and the centrosome. A role for TCP-1 in microtubule nucleation. The Journal of biological chemistry 74 8557692
1995 The eighth Cct gene, Cctq, encoding the theta subunit of the cytosolic chaperonin containing TCP-1. Gene 74 7890169
1987 The human homologue of the mouse t-complex gene, TCP1, is located on chromosome 6 but is not near the HLA region. The EMBO journal 73 3653076
2014 Chaperonin containing TCP1, subunit 8 (CCT8) is upregulated in hepatocellular carcinoma and promotes HCC proliferation. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 60 24862099
1994 Primary structure and function of a second essential member of the heterooligomeric TCP1 chaperonin complex of yeast, TCP1 beta. Proceedings of the National Academy of Sciences of the United States of America 59 7908441
2017 Targeting chaperonin containing TCP1 (CCT) as a molecular therapeutic for small cell lung cancer. Oncotarget 54 29299146
1995 Antibody characterisation of two distinct conformations of the chaperonin-containing TCP-1 from mouse testis. FEBS letters 52 7828721
1997 Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1. FEBS letters 51 9013858
2016 Chaperonin Containing TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide. Clinical cancer research : an official journal of the American Association for Cancer Research 48 27012814
2009 Intracellular beta-tubulin/chaperonin containing TCP1-beta complex serves as a novel chemotherapeutic target against drug-resistant tumors. Cancer research 48 19690144
1998 The chaperone cofactor Hop/p60 interacts with the cytosolic chaperonin-containing TCP-1 and affects its nucleotide exchange and protein folding activities. The Journal of biological chemistry 47 9792653
2003 Cct1, a phosphatidylcholine biosynthesis enzyme, is required for Drosophila oogenesis and ovarian morphogenesis. Development (Cambridge, England) 46 14597574
2010 Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl. Proceedings of the National Academy of Sciences of the United States of America 45 21098288
1999 Origin of gene overlap: the case of TCP1 and ACAT2. Genetics 43 10353914
2020 Investigating Chaperonin-Containing TCP-1 subunit 2 as an essential component of the chaperonin complex for tumorigenesis. Scientific reports 39 31964905
1995 Conformational cycle of the archaeosome, a TCP1-like chaperonin from Sulfolobus shibatae. The Journal of biological chemistry 39 7499406
1993 A TCP1-related molecular chaperone from plants refolds phytochrome to its photoreversible form. Nature 37 8099715
1990 Expression of three t-complex genes, Tcp-1, D17Leh117c3, and D17Leh66, in purified murine spermatogenic cell populations. Genetical research 36 2272510
2012 Cytotoxin CctA, a major virulence factor of Clostridium chauvoei conferring protective immunity against myonecrosis. Vaccine 34 22749595
1992 Structure and expression of the gene encoding mouse t-complex polypeptide (Tcp-1). Gene 32 1383093
1998 The chaperonin containing TCP-1 (CCT) displays a single-ring mediated disassembly and reassembly cycle. Biological chemistry 31 9563827
2021 TCP1 increases drug resistance in acute myeloid leukemia by suppressing autophagy via activating AKT/mTOR signaling. Cell death & disease 30 34750375
1994 Identification of the major chromaffin granule-binding protein, chromobindin A, as the cytosolic chaperonin CCT (chaperonin containing TCP-1). The Journal of biological chemistry 30 7798195
2021 Heightened splenic and bone marrow uptake of 18F-FDG PET/CT is associated with systemic inflammation and subclinical atherosclerosis by CCTA in psoriasis: An observational study. Atherosclerosis 28 34808541
2018 The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its mechanism that folds actin into a protein spring. The Biochemical journal 28 30291170
2013 Isolation and characterization of a novel Dehalobacter species strain TCP1 that reductively dechlorinates 2,4,6-trichlorophenol. Biodegradation 28 23995979
2012 Regulation of nuclear factor κB (NF-κB) transcriptional activity via p65 acetylation by the chaperonin containing TCP1 (CCT). PloS one 27 22860050
2010 Disruption of the chaperonin containing TCP-1 function affects protein networks essential for rod outer segment morphogenesis and survival. Molecular & cellular proteomics : MCP 27 20852191
1996 Peptide mass fingerprinting of chaperonin-containing TCP-1 (CCT) and copurifying proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 8566534
2015 TCP1 Modulates DWF4 Expression via Directly Interacting with the GGNCCC Motifs in the Promoter Region of DWF4 in Arabidopsis thaliana. Journal of genetics and genomics = Yi chuan xue bao 26 26233893
2000 Transcriptional regulation of the mouse cytosolic chaperonin subunit gene Ccta/t-complex polypeptide 1 by selenocysteine tRNA gene transcription activating factor family zinc finger proteins. The Journal of biological chemistry 26 10893243
1994 TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix. Journal of cell science 26 7876352
2017 Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth. Oncotarget 25 29340068
2021 Chaperonin-Containing TCP1 Complex (CCT) Promotes Breast Cancer Growth Through Correlations With Key Cell Cycle Regulators. Frontiers in oncology 24 33996588
2017 Genetic expansion of chaperonin-containing TCP-1 (CCT/TRiC) complex subunits yields testis-specific isoforms required for spermatogenesis in planarian flatworms. Molecular reproduction and development 24 29095551
1992 Cloning of a cDNA encoding the Tcp-1 (t complex polypeptide 1) homologue of Arabidopsis thaliana. Gene 24 1487154
2020 Chaperonin-Containing TCP-1 Promotes Cancer Chemoresistance and Metastasis through the AKT-GSK3β-β-Catenin and XIAP-Survivin Pathways. Cancers 23 33371405
2015 Misato Controls Mitotic Microtubule Generation by Stabilizing the TCP-1 Tubulin Chaperone Complex [corrected]. Current biology : CB 23 26096973
2017 Chaperonin containing TCP1 subunit 5 is a tumor associated antigen of non-small cell lung cancer. Oncotarget 21 28969060
2008 Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin. Journal of the Royal Society, Interface 21 18708324
1987 Assignment of the TCP1 locus to the long arm of human chromosome 6 by in situ hybridization. Cytogenetics and cell genetics 21 3476253
1990 Cloning of a Chinese hamster protein homologous to the mouse t-complex protein TCP-1: structural similarity to the ubiquitous 'chaperonin' family of heat-shock proteins. Biochimica et biophysica acta 20 1977474
1988 Genetic polymorphism of a bovine t-complex gene (TCP1) linkage to major histocompatibility genes. The Journal of heredity 20 2896675
2021 Chaperonin containing TCP1 subunit 3 (CCT3) promotes cisplatin resistance of lung adenocarcinoma cells through targeting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. Bioengineered 19 34612768
2007 Conformational rearrangements of tail-less complex polypeptide 1 (TCP-1) ring complex (TRiC)-bound actin. Biochemistry 17 17417821
1997 Developmental and light-dependent changes of the cytosolic chaperonin containing TCP-1 (CCT) subunits in maize seedlings, and the localization in coleoptiles. The Plant journal : for cell and molecular biology 17 9450343
1994 Functional role of a consensus peptide which is common to alpha-, beta-, and gamma-tubulin, to actin and centractin, to phytochrome A, and to the TCP1 alpha chaperonin protein. FEBS letters 17 8033985
2021 TCP1 regulates PI3K/AKT/mTOR signaling pathway to promote proliferation of ovarian cancer cells. Journal of ovarian research 16 34162426
2006 Affinity purification reveals the association of WD40 protein constitutive photomorphogenic 1 with the hetero-oligomeric TCP-1 chaperonin complex in mammalian cells. The international journal of biochemistry & cell biology 16 16497536
2006 Characterization of the cytoplasmic chaperonin containing TCP-1 from the Antarctic fish Notothenia coriiceps. Extremophiles : life under extreme conditions 15 16770691
1997 Subunit characterization of the Caenorhabditis elegans chaperonin containing TCP-1 and expression pattern of the gene encoding CCT-1. Biochemical and biophysical research communications 15 9434769
1993 Two acetyl-CoA acetyltransferase genes located in the t-complex region of mouse chromosome 17 partially overlap the Tcp-1 and Tcp-1x genes. Genomics 15 7904580
2023 Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma. Cancer biology & therapy 14 38084868
2020 Avian Chaperonin Containing TCP1 Subunit 5 Supports Influenza A Virus Replication by Interacting With Viral Nucleoprotein, PB1, and PB2 Proteins. Frontiers in microbiology 14 33178142
2014 Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor. FEBS letters 14 24846140
2011 TCP1 positively regulates the expression of DWF4 in Arabidopsis thaliana. Plant signaling & behavior 14 21822059
1997 Rat chromosome 1: regional localization of seven genes (Slc9a3, Srd5a1, Esr, Tcp1, Grik5, Tnnt3, Jak2) and anchoring of the genetic linkage map to the cytogenetic map. Mammalian genome : official journal of the International Mammalian Genome Society 14 9271667
1992 Genetic mapping of three human homologues of murine t-complex genes localizes TCP10 to 6q27, 15 cM distal to TCP1 and PLG. Genomics 14 1572657
1998 A Dictyostelium discoideum homologue to Tcp-1 is essential for growth and development. Gene 13 9630545
1996 Analysis of chaperonin-containing TCP-1 subunits in the human keratinocyte two-dimensional protein database: further characterisation of antibodies to individual subunits. Electrophoresis 13 8982604
1995 Molecular analysis of Caenorhabditis elegans tcp-1, a gene encoding a chaperonin protein. Gene 13 7758963
1994 The amino acid sequence previously attributed to a protein kinase or a TCP1-related molecular chaperone and co-purified with phytochrome is a beta-glucosidase. FEBS letters 13 8013661
2006 Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity. Cellular and molecular life sciences : CMLS 11 16568240
1991 Cloning of cDNA encoding rat TCP-1. Biochimica et biophysica acta 10 1756183
2022 Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma. Frontiers in oncology 9 36185250
2021 Resistance of Acta2R149C/+ mice to aortic disease is associated with defective release of mutant smooth muscle α-actin from the chaperonin-containing TCP1 folding complex. The Journal of biological chemistry 9 34600884
2010 Sirt1’s beneficial roles in neurodegenerative diseases - a chaperonin containing TCP-1 (CCT) connection? Aging cell 9 20569238
1985 Expression of the Tcp-1 locus of the mouse during early embryogenesis. Journal of embryology and experimental morphology 9 4093742
1994 cDNA encoding a novel TCP1-related protein. Biochimica et biophysica acta 8 8110840
2024 METTL14-mediated N6-methyladenosine modification of TCP1 mRNA promotes acute myeloid leukemia progression. Cellular signalling 7 39033992
2015 Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis. Oncotarget 7 26556873
2013 OMICS in ecology: systems level analyses of Halobacterium salinarum reveal large-scale temperature-mediated changes and a requirement of CctA for thermotolerance. Omics : a journal of integrative biology 7 24147786
2024 Chaperonin-containing TCP1 subunit 6A inhibition via TRIM21-mediated K48-linked ubiquitination suppresses triple-negative breast cancer progression through the AKT signalling pathway. Clinical and translational medicine 6 39556022
2022 Unraveling of interacting protein network of chaperonin TCP1 gamma subunit of Leishmania donovani. Cell stress & chaperones 6 35199315
2020 The Putative TCP-1 Chaperonin Is an Important Player Involved in Sialic Acid-Dependent Host Cell Invasion by Toxoplasma gondii. Frontiers in microbiology 6 32153542
2025 TCP1 promotes the progression of malignant tumours by stabilizing c-Myc through the AKT/GSK-3β and ERK signalling pathways. Communications biology 5 40185866
2015 Gpd1 Regulates the Activity of Tcp-1 and Heat Shock Response in Yeast Cells: Effect on Aggregation of Mutant Huntingtin. Molecular neurobiology 5 26164272
2025 Role of the chaperonin TCP-1 ring complex in protein aggregation and neurodegeneration. Frontiers in molecular neuroscience 4 40693240
2022 Association between major adverse cardiovascular events and pentraxin-3 in patients who have undergone coronary computed tomography angiography: from the FU-CCTA registry. Heart and vessels 4 36169707
1992 Nucleotide sequence of a mouse Tcp-1 pseudogene: a nucleotide record for a t complex gene carried by an ancestor of the mouse. Mammalian genome : official journal of the International Mammalian Genome Society 4 1543916