Eukaryotic type II chaperonin CCT interacts with actin through specific subunits

Llorca, Óscar; McCormack, Elizabeth A.; Hynes, Gillian; Grantham, Julie; Cordell, Jacqueline; Carrascosa, José L.; Willison, Keith R.; Fernández, Julio F.; Valpuesta, José M.

doi:10.1038/45294

Cited by 247 publications

(349 citation statements)

References 17 publications

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“…Interestingly, Group II chaperonins share sequence homology with GroEL at the ATP binding site, but they differ considerably in sequence of the substrate binding site (Kim et al, 1994;Spiess et al, 2006). TRiC, like GroEL, is an essential protein since at least two cytoskeletal proteins, actin and tubulin, are obligate substrates of TRiC (Dobrzynski et al, 1996;Gao et al, 1992;Llorca et al, 1999;Yaffe et al, 1992). Unlike GroEL/ES which can act only post-translationally, TRiC has been shown to fold the discrete domains of firefly luciferase co-translationally (Frydman et al, 1994).…”

Section: Ii4113 the Chaperoninsmentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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Section: Ii4113 the Chaperoninsmentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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“…CCT is an essential chaperone of protein folding found in the cytosol of eukaryotic cells [70,71]. It consists of eight different but related subunits of ∼ 60 kDa packed together to form a ring structure [72]. Two identical rings stack on top of each other to form the holo-CCT complex of sixteen subunits [72].…”

Section: Over-turning the Paradigm -Phlp1 As An Essential Co-chaperonmentioning

confidence: 99%

“…It consists of eight different but related subunits of ∼ 60 kDa packed together to form a ring structure [72]. Two identical rings stack on top of each other to form the holo-CCT complex of sixteen subunits [72]. Nascent polypeptides and denatured proteins associate in a large cavity formed in the center of each eight-membered ring [72].…”

Section: Over-turning the Paradigm -Phlp1 As An Essential Co-chaperonmentioning

confidence: 99%

“…Two identical rings stack on top of each other to form the holo-CCT complex of sixteen subunits [72]. Nascent polypeptides and denatured proteins associate in a large cavity formed in the center of each eight-membered ring [72]. Amino acid residues within the ring make contacts with the unfolded protein and decrease the activation energy required to form the three-dimensional structure of the native protein [73].…”

Section: Over-turning the Paradigm -Phlp1 As An Essential Co-chaperonmentioning

confidence: 99%

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Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding

Willardson

Howlett

2007

Cellular Signalling

101

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Members of the phosducin gene family were initially proposed to act as down-regulators of G protein signaling by binding G protein βγ dimers (Gβγ) and inhibiting their ability to interact with G protein α subunits (Gα) and effectors. However, recent findings have overturned this hypothesis by showing that most members of the phosducin family act as cochaperones with the cytosolic chaperonin complex (CCT) to assist in the folding of a variety of proteins from their nascent polypeptides. In fact rather than inhibiting G protein pathways, phosducin-like protein 1 (PhLP1) has been shown to be essential for G protein signaling by catalyzing the folding and assembly of the Gβγ dimer. PhLP2 and PhLP3 have no role in G protein signaling, but they appear to assist in the folding of proteins essential in regulating cell cycle progression as well as actin and tubulin. Phosducin itself is the only family member that does not participate with CCT in protein folding, but it is believed to have a specific role in visual signal transduction to chaperone Gβγ subunits as they translocate to and from the outer and inner segments of photoreceptor cells during light-adaptation.

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“…A group II chaperonin, chaperonin containing t-complex polypeptide 1 (CCT, also called TRiC), has been identified in the eukaryotic cytosol (Kubota, 2002;Spiess et al, 2004). CCT is a hexadecameric complex composed of eight different subunits (Kubota et al, 1994;Llorca et al, 1999) and facilitates protein folding (Tian et al, 1995;Farr et al, 1997;Meyer et al, 2003;Kubota et al, 2006). Recently, CCT was shown to inhibit protein aggregation and counteract the cytotoxicity of misfolded proteins (Behrends et al, 2006;Kitamura et al, 2006;Kubota et al, 2006;Tam et al, 2006).…”

mentioning

confidence: 99%

MKKS Is a Centrosome-shuttling Protein Degraded by Disease-causing Mutations via CHIP-mediated Ubiquitination

Hirayama

Yamazaki²,

Kitamura³

et al. 2008

MBoC

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McKusick-Kaufman syndrome (MKKS) is a recessively inherited human genetic disease characterized by several developmental anomalies. Mutations in the MKKS gene also cause Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder with pleiotropic symptoms. However, little is known about how MKKS mutations lead to disease. Here, we show that disease-causing mutants of MKKS are rapidly degraded via the ubiquitin-proteasome pathway in a manner dependent on HSC70 interacting protein (CHIP), a chaperone-dependent ubiquitin ligase. Although wild-type MKKS quickly shuttles between the centrosome and cytosol in living cells, the rapidly degraded mutants often fail to localize to the centrosome. Inhibition of proteasome functions causes MKKS mutants to form insoluble structures at the centrosome. CHIP and partner chaperones, including heat-shock protein (HSP)70/heat-shock cognate 70 and HSP90, strongly recognize MKKS mutants. Modest knockdown of CHIP by RNA interference moderately inhibited the degradation of MKKS mutants. These results indicate that the MKKS mutants have an abnormal conformation and that chaperone-dependent degradation mediated by CHIP is a key feature of MKKS/BBS diseases. INTRODUCTIONMcKusick-Kaufman syndrome (MKKS) is a recessively inherited human genetic disease predominantly characterized by developmental anomalies, including vaginal atresia with hydrometrocolpos, polydactyly, and congenital heart defects (McKusick et al., 1964). The MKKS gene encodes a 570-amino acid polypeptide with weak but significant similarity to group II chaperonins . Mutations in the MKKS gene also cause Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder characterized by obesity, retinal dystrophy, polydactyly, mental retardation, renal malformation, and hypogenitalism (Beales et al., 1999), and thus MKKS is also called BBS6. The MKKS mRNA is widely expressed in various tissues, including those affected by MKKS and BBS diseases . Although more than 10 mutations in the MKKS gene have been identified in patients (Beales et al., 2001;Slavotinek et al., 2002), little is known about how they cause MKKS and BBS.Twelve of the genes that are responsible for BBS (BBS1-12) have been identified so far, and the products of several of these genes have been suggested to be involved in intraflagellar transport in cilia and intracellular trafficking in the cytosol Badano et al., 2005;Beales, 2005;Blacque and Leroux, 2006). Cargo-carrying motors play crucial roles in intraflagellar and intracellular transport systems by bidirectionally moving on microtubules, and BBS4 interacts with the dynactin complex, which mediates interactions between cargoes and the dynein motor (Kim et al., 2004). Retrograde transport of melanosomes in zebrafish is slowed by knockdown of BBS2 or BBS4-8 (Yen et al., 2006), whereas mutations in Caenorhabditis elegans BBS7 and BBS8 cause delays in intraflagellar transport driven by kinesin motors (Ou et al., 2005). The Chlamydomonas homologue of BBS5 is essential for flagellum formation (Li et al., ...

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Eukaryotic type II chaperonin CCT interacts with actin through specific subunits

Cited by 247 publications

References 17 publications

Firefly luciferase mutants as sensors of proteome stress

Firefly luciferase mutants as sensors of proteome stress

Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding

MKKS Is a Centrosome-shuttling Protein Degraded by Disease-causing Mutations via CHIP-mediated Ubiquitination

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