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dc.contributor.authorAmit, Men_US
dc.contributor.authorWeisberg, SJen_US
dc.contributor.authorNadler-Holly, Men_US
dc.contributor.authorMcCormack, EAen_US
dc.contributor.authorFeldmesser, Een_US
dc.contributor.authorKaganovich, Den_US
dc.contributor.authorWillison, KRen_US
dc.contributor.authorHorovitz, Aen_US
dc.identifier.citationJOURNAL OF MOLECULAR BIOLOGY, 2010, 401 pp. 532 - 543en_US
dc.description.abstractThe eukaryotic cytoplasmic chaperonin-containing TCP-1 (CCT) is a complex formed by two back-to-back stacked hetero-octameric rings that assists the folding of actins, tubulins, and other proteins in an ATP-dependent manner. Here, we tested the significance of the hetero-oligomeric nature of CCT in its function by introducing, in each of the eight subunits in turn, an identical mutation at a position that is conserved in all the subunits and is involved in ATP hydrolysis, in order to establish the extent of ‘individuality’ of the various subunits. Our results show that these identical mutations lead to dramatically different phenotypes. For example, Saccharomyces cerevisiae yeast cells with the mutation in subunit CCT2 display heat sensitivity and cold sensitivity for growth, have an excess of actin patches, and are the only strain here generated that is pseudo-diploid. By contrast, cells with the mutation in subunit CCT7 are the only ones to accumulate juxtanuclear protein aggregates that may reflect an impaired stress response in this strain. System-level analysis of the strains using RNA microarrays reveals connections between CCT and several cellular networks, including ribosome biogenesis and TOR2, that help to explain the phenotypic variability observed. (C) 2010 Elsevier Ltd. All rights reserved.en_US
dc.format.extent532 - 543en_US
dc.titleEquivalent Mutations in the Eight Subunits of the Chaperonin CCT Produce Dramatically Different Cellular and Gene Expression Phenotypesen_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.notesaffiliation: Horovitz, A (Reprint Author), Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. Amit, Maya; Weisberg, Sarah J.; Nadler-Holly, Michal; Horovitz, Amnon, Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. McCormack, Elizabeth A.; Willison, Keith R., Inst Canc Res, Chester Beatty Labs, Sect Cell & Mol Biol, London SW3 6JB, England. Feldmesser, Ester, Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel. Kaganovich, Daniel, Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. keywords: molecular chaperones; chaperonins; RNA microarrays; structure-function analysis; aggregation keywords-plus: EUKARYOTIC CHAPERONIN; SACCHAROMYCES-CEREVISIAE; ATP HYDROLYSIS; IN-VIVO; YEAST; ACTIN; PROTEIN; TRIC/CCT; SYSTEMS; BINDING research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology author-email: [email protected] researcherid-numbers: Kaganovich, Daniel/K-2376-2012 orcid-numbers: Kaganovich, Daniel/0000-0003-2398-1596 funding-acknowledgement: Israel Science Foundation [153/08]; Cancer Research UK funding-text: We thank Dr. Hagai Abeliovich, Dr. Ghil Jona, and Gillian Hynes for helpful advice, and Dr. Yoav Peleg for help with the cloning of the CCT8 gene. M.A. received a short-term EMBO fellowship. This work was supported by grant 153/08 from the Israel Science Foundation (A.H.) and by Cancer Research UK (K.R.W.). A.H. is an incumbent of the Carl and Dorothy Bennett Professorial Chair in Biochemistry. number-of-cited-references: 41 times-cited: 38 usage-count-last-180-days: 0 usage-count-since-2013: 6 journal-iso: J. Mol. Biol. doc-delivery-number: 641ZB unique-id: ISI:000281171000016 da: 2018-08-21en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Chromatin Regulation
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Wigley Group
pubs.embargo.termsNot knownen_US
icr.researchteamChromatin Regulationen_US
icr.researchteamWigley Groupen_US
dc.contributor.icrauthorMccormack, Elizabeth Anneen_US
dc.contributor.icrauthorWillison, Keithen_US

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