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Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation.

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Cell Stress and Chaperones Aims and scope

Abstract

The chaperonin containing TCP-1 (CCT) is required for the production of native actin and tubulin and numerous other proteins, several of which are involved in cell cycle progression. The mechanistic details of how CCT acts upon its folding substrates are intriguing: whilst actin and tubulin bind in a sequence-specific manner, it is possible that some proteins could use CCT as a more general binding interface. Therefore, how CCT accommodates the folding requirements of its substrates, some of which are produced in a cell cycle-specific manner, is of great interest. The reliance of folding substrates upon CCT for the adoption of their native structures results in CCT activity having far-reaching implications for a vast array of cellular processes. For example, the dependency of the major cytoskeletal proteins actin and tubulin upon CCT results in CCT activity being linked to any cellular process that depends on the integrity of the microfilament and microtubule-based cytoskeletal systems.

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References

  • Arava Y, Wang Y, Storey JD, Liu CL, Brown PO, Herschlag D (2003) Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 100:3889–3894

    Article  PubMed  CAS  Google Scholar 

  • Behrends C, Langer CA, Boteva R et al (2006) Chaperonin TRiC promotes the assembly of polyQ expansion proteins into non toxic oligomers. Mol Cell 23:887–897

    Article  PubMed  CAS  Google Scholar 

  • Brown CR, Doxsey SJ, Hong-Brown LQ, Martin RL, Welch WJ (1996) Molecular chaperones and the centrosome: a role for TCP-1 in microtubule nucleation. J Biol Chem 271:824–832

    Article  PubMed  CAS  Google Scholar 

  • Camasses A, Bogdanova A, Shevchenko A, Zachariae W (2003) The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol Cell 12:87–100

    Article  PubMed  CAS  Google Scholar 

  • Cleveland DW, Sullivan KF (1985) Molecular biology and genetics of tubulin. Ann Rev Biochem 54:331–366

    Article  PubMed  CAS  Google Scholar 

  • Ellis RJ (1996) Revisiting the Anfinsen cage. Fold Des 1:R9–R15

    Article  PubMed  CAS  Google Scholar 

  • Futcher B, Latter GI, Monardo P, Mclaughlin CS, Garrels JI (1999) A sampling of the yeast proteome. Mol Cell Biol 19:7357–7368

    PubMed  CAS  Google Scholar 

  • Gomez-Puertas P, Martin-Benito J, Carrascosa JL, Willison KR, Valpuesta JM (2004) The substrate recognition mechanisms in chaperonins. J Mol Recognit 17:85–94

    Article  PubMed  CAS  Google Scholar 

  • Grantham J, Llorca O, Valpuesta JM, Willison KR (2000) Partial occlusion of both cavities of the eukaryotic chaperonin with antibody has no effect upon the rates of beta-actin or alpha-tubulin folding. J Biol Chem. 275:4587–4591

    Article  PubMed  CAS  Google Scholar 

  • Grantham J, Ruddock LW, Roobol A, Carden MJ (2002) Eukaryotic chaperonin containing T-complex polypeptide 1 interacts with filamentous actin and reduces the initial rate of actin polymerization in vitro. Cell Stress Chaperones 7:235–242

    Article  PubMed  CAS  Google Scholar 

  • Grantham J, Brackley KI, Willison KR (2006) Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells. Exp Cell Res 312:2309–2324

    Article  PubMed  CAS  Google Scholar 

  • Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858

    Article  PubMed  CAS  Google Scholar 

  • Horwich AL, Fenton WA, Chapman E, Farr GW (2007) Two families of chaperonin: physiology and mechanism. Annu Rev Cell Dev Biol 23:115–145

    Article  PubMed  CAS  Google Scholar 

  • Horwich AL, Low KB, Fenton WA, Hirshfield IN, Furtak K (1993) Folding in vivo of bacterial cytoplasmic proteins: role of GroEL. Cell 74:909–917

    Article  PubMed  CAS  Google Scholar 

  • Hynes GM, Willison KR (2000) Individual subunits of the eukaryotic cytosolic chaperonin mediate interactions with binding sites located on subdomains of beta-actin. J Biol Chem 275:18985–18994

    Article  PubMed  CAS  Google Scholar 

  • Kabir MA, Kaminska J, Segel GB et al (2005) Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae. Yeast 22:219–239

    Article  PubMed  CAS  Google Scholar 

  • Kitamura A, Kubota H, Pack C-G et al (2006) Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol 8:1163–1170

    Article  PubMed  CAS  Google Scholar 

  • Lacefield S, Soloman F (2003) A novel step in beta-tubulin folding is important for heterodimer formation in Saccharomyces cerevisiae. Genetics 165:531–541

    PubMed  CAS  Google Scholar 

  • Lackner DH, Beilharz TH, Marguerat S, Mata S, Watt S, Schubert F, Preiss T, Bähler J (2007) A network of multiple regulatory layers shapes gene expression in fisson yeast. Mol Cell 26:145–155

    Article  PubMed  CAS  Google Scholar 

  • Lewis SA, Tian G, Cowan NJ (1997) The alpha- and beta-tubulin folding pathways. Trends Cell Biol 7:479–484

    Article  PubMed  CAS  Google Scholar 

  • Lin P, Sherman F (1997) The unique hetero-oligomeric nature of the subunits in the catalytic cooperativity of the yeast Cct chaperonin complex. Proc Natl Acad Sci U S A 94:10780–10785

    Article  PubMed  CAS  Google Scholar 

  • Liou AKF, Willison KR (1997) Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from the subunit composition of CCT micro-complexes. EMBO J 16:4311–4316

    Article  PubMed  CAS  Google Scholar 

  • Liou AKF, McCormack EA, Willison KR (1998) The chaperonin containing TCP-1 (CCT) displays a single-ring mediated disassembly and reassembly cycle. Biol Chem 379:311–319

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Lin C-Y, Lei M, Lan S, Zhou T, Erikson RL (2005) CCT chaperonin complex is required for the biogenesis of functional Plk1. Mol Cell Biol 25:4993–5010

    Article  PubMed  CAS  Google Scholar 

  • Llorca O, McCormack EA, Hynes G et al (1999) Eukaryotic type II chaperonin CCT interacts with actin through specific subunits. Nature 402:693–696

    Article  PubMed  CAS  Google Scholar 

  • Llorca O, Martin-Benito J, Ritco-Vonsovici M, Grantham J, Hynes GM, Willison KR, Carrascosa JL, Valpuesta JM (2000) Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations. EMBO J 19:5971–5979

    Article  PubMed  CAS  Google Scholar 

  • Llorca O, Martin-Benito J, Grantham J, Ritco-Vonsovici M, Willison KR, Carrascosa JL Valpuesta JM (2001) The ‘sequential allosteric ring’ mechanism in the eukaryotic chaperonin- assisted folding of actin and tubulin. EMBO J 20:4065–4075

    Article  PubMed  CAS  Google Scholar 

  • Martin-Benito J, Bertrand S, Hu T, Ludtke PJ, McLaughlin JN, Willardson BM, Carrascosa JL, Valpuesta JM (2004) Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein. Proc Natl Acad Sci U S A 101:17410–17415

    Article  PubMed  CAS  Google Scholar 

  • Martin-Benito J, Grantham J, Boskovic J, Brackley KI, Carrascosa JL, Willison KR, Valpuesta JM (2007) The inter-ring arrangement of the cytosolic chaperonin CCT. EMBO Rep 8:252–257

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin JN, Thulin CD, Hart SJ, Resing KA, Ahn NG, Willardson BM (2002) Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex. Proc Natl Acad Sci U S A 99:7962–7967

    Article  PubMed  CAS  Google Scholar 

  • Melki R, Batelier G, Soulie S, Williams RC (1997) Cytoplasmic chaperonin containing TCP-1: structural and functional characterisation. Biochemistry 36:5817–5826

    Article  PubMed  CAS  Google Scholar 

  • Mellville MW, McClellan AJ, Meyer AS, Darveau A, Frydman J (2003) The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Linau tumor suppressor complex. Mol Cell Biol 23:3141–3151

    Article  CAS  Google Scholar 

  • Neirynck K, Waterschoot D, Vandekerckhove J, Ampe C, Rommelaere H (2006) Actin interacts with CCT via discrete binding sites: a binding transition-release model for CCT mediated actin folding. J Mol Biol 355:124–138

    Article  PubMed  CAS  Google Scholar 

  • Pappenberger G, Wilsher JA, Roe SM, Counsell DJ, Willison KR, Pearl LH (2002) Crystal structure of the CCTgamma apical domain: implications for substrate binding to the eukaryotic cytosolic chaperonin. J Mol Biol 318:1367–1379

    Article  PubMed  CAS  Google Scholar 

  • Pappenberger G, McCormack EA, Willison KR (2006) Quantitative actin folding reactions using yeast CCT purified via an internal tag in the CCT3/γ subunit. J Mol Biol 360:484–496

    Article  PubMed  CAS  Google Scholar 

  • Passmore LA, McCormack EA, Au SWN, Paul A, Willison KR, Harper JW, Barford D (2003) Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J 22:786–796

    Article  PubMed  CAS  Google Scholar 

  • Posern G, Triesman R (2006) Actin’ together: serum response factor, its cofactors and the link to signal transduction. Trends Cell Biol 16:588–596

    Article  PubMed  CAS  Google Scholar 

  • Rademacher F, Kehren V, Stoldt VR, Ernst JF (1998) A Candida albicans chaperonin subunit (CaCct8p) as a suppressor of morphogenesis and Ras phenotypes in C. albicans and Saccharomyces cerevisiae. Microbiology 144:2951–2960

    Article  PubMed  CAS  Google Scholar 

  • Roobol A, Holmes FE, Hayes NVL, Baines AJ, Carden MJ (1995) Cytoplasmic chaperonin complexes enter neurites developing in vitro and differ in subunit composition within single cells. J Cell Sci 108:1477–1488

    PubMed  CAS  Google Scholar 

  • Roobol A, Grantham J, Whitaker HC, Carden MJ (1999a) Disassembly of the cytosolic chaperonin in mammalian cell extracts at intracellular levels of K + and ATP. J Biol Chem 274:19220–19227

    Article  PubMed  CAS  Google Scholar 

  • Roobol A, Sahyoun ZP, Carden MJ (1999b) Selected subunits of the cytosolic chaperonin associate with microtubules assembled in vitro. J Biol Chem 274:2408–2415

    Article  PubMed  CAS  Google Scholar 

  • Rivenzon-Segal D, Wolf SG, Shimon L, Willison KR, Horovitz A (2005) Sequential ATP-induced allosteric transitions of the cytoplasmic chaperonin containing TCP-1 revealed by EM analysis. Nat Struct Biol 12:233–237

    Article  CAS  Google Scholar 

  • Shimon L, Hynes GM, McCormack EA, Willison KR Horovitz A (2008) ATP-induced allostery in the eukaryotic chaperonin CCT is abolished by the mutation G345D in CCT4 that renders yeast temperature sensitive for growth. J Mol Biol 377:469–477

    Article  PubMed  CAS  Google Scholar 

  • Soues S, Kann M-L, Fouquet J-P, Melki R (2003) The cytosolic chaperonin CCT associates to cytoplasmic microtubular structures during mammalian spermiogenesis and to heterochromatin in germline and somatic cells. Exp Cell Res 288:363–373

    Article  PubMed  CAS  Google Scholar 

  • Srikakulam R, Winkelmann DA (1999) Myosin II folding is mediated by a molecular chaperonin. J Biol Chem 274:27265–27273

    Article  PubMed  CAS  Google Scholar 

  • Stemp MJ, Guha S, Hartl FU, Barral JM (2005) Efficient production of native actin upon translation in a bacterial lysate supplemented with the eukaryotic chaperonin TRiC. Biol Chem 386:753–757

    Article  PubMed  CAS  Google Scholar 

  • Sternlicht H, Farr GW, Sternlicht ML, Driscoll JK, Willison K, Yaffe MB (1993) The t-complex polypeptide 1 is a chaperonin for tubulin and actin in vivo. Proc Natl Acad Sci U S A 90:9422–9426

    Article  PubMed  CAS  Google Scholar 

  • Stirling PC, Cuellar J, Alfaro GA, Khadali FE, Beh CT, Valpuesta JM, Melki R, Leroux MR (2006) PhLP3 Modulates CCT-mediated actin and tubulin folding via ternary complexes with substrate. J Biol Chem 281:7012–7021

    Article  PubMed  CAS  Google Scholar 

  • Stirling PC, Srayko M, Takhar KS, Pozniakovsky A, Hyman AA, Leroux MR (2007) Functional interaction between Phosducin-like Protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression. Mol Biol Cell 18:2336–2345

    Article  PubMed  CAS  Google Scholar 

  • Stoldt V, Rademacher F, Kehren V, Ernst JF, Pearce DA, Sherman F (1996) Review: the Cct eukaryotic chaperonin subunits of Saccharomyces cerevisiae and other yeasts. Yeast 12:523–529

    Article  PubMed  CAS  Google Scholar 

  • Tam S, Geller R, Speiss C, Frydman J (2006) The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat Cell Biol 8:1155–1162

    Article  PubMed  CAS  Google Scholar 

  • Valpuesta JM, Martin-Benito J, Gomez-Puertas P, Carrascosa JL, Willison KR (2002) Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett 529:11–16

    Article  PubMed  CAS  Google Scholar 

  • Vinh DB, Drubin DG (1994) A yeast TCP-1-like protein is required for actin function in vivo. Proc Natl Acad Sci U S A 91:9116–9120

    Article  PubMed  CAS  Google Scholar 

  • Weinstein B, Soloman F (1990) Phenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin. Mol Cell Biol 10:5295–5304

    PubMed  CAS  Google Scholar 

  • Weissman JS, Hohl CM, Kovalenko O et al (1995) Mechanism of GroEL action: productive release of polypeptide from a sequestered position under GroES. Cell 83:577–587

    Article  PubMed  CAS  Google Scholar 

  • Willardson BM, Howlett AC (2007) Function of phosducin-like proteins in G protein signalling and chaperone assisted folding. Cell Signal 19:2417–2427

    Article  PubMed  CAS  Google Scholar 

  • Won KA, Schumacher RJ, Farr GW, Horwich AL, Reed SI (1998) Maturation of human cyclin E requires the function of eukaryotic chaperonin CCT. Mol Cell Biol 18:7584–7589

    PubMed  CAS  Google Scholar 

  • Yokota S, Yanagi H, Yura T, Kubota H (1999) Cytosolic chaperonin is up-regulated during cell growth. J Biol Chem 274:37070–37078

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We acknowledge grants from Vetenskapsrådet, Assar Gabrielssons Fond and Carl Tryggers Stiftelse. We thank Thomas Nyström for comments on the manuscript and Per Sunnerhagen for helpful discussions.

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Correspondence to Julie Grantham.

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Brackley, K.I., Grantham, J. Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation.. Cell Stress and Chaperones 14, 23–31 (2009). https://doi.org/10.1007/s12192-008-0057-x

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