The 90-kilodalton peptide of the heme-regulated eIF-2.alpha. kinase has sequence homology with the 90-kilodalton heat shock protein

Rose, David W.; Wettenhall, Richard E.H.; Kudlicki, Wiesław; Kramer, Gisela; Hardesty, Boyd

doi:10.1021/bi00395a003

Cited by 129 publications

(61 citation statements)

References 35 publications

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“…3b. Judging from these data and from studies in other laboratories on hsp90 interactions (4,18,24,33), it is likely that additional proteins less abundant than the identified spots in Fig. 3 to 100% (peptide 3).…”

Section: Methodsmentioning

confidence: 75%

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Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.

et al. 1993

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Immunoaffinity purification of hsp90 from chick oviduct cytosol reveals two major proteins, hsp70 and a 60-kDa protein (p60), copurifying with hsp90. A similar result is obtained when hsp90 is immunoaffinity purified from chick liver and brain cytosols, avian fibroblasts, and rabbit reticulocyte lysate. This p60 is the same protein previously identified in certain assembly complexes of chick progesterone receptor generated in a cell-free reconstitution system. Tryptic and cyanogen bromide peptide fragments were generated from gel-purified p60, and partial N-terminal sequences were determined from eight peptides. The sequences show a striking similarity to the sequence of a 63-kDa human protein (IEF SSP 3521) whose abundance is increased in MRC-5 fibroblasts following simian virus 40 transformation. A monoclonal antibody was prepared against avian p60; Western immunoblot analysis showed that p60 was present in each of eight chick tissues examined and in each of the human, rat, rabbit, andXenopus tissues tested. Immunoaffinity purifications from both chick oviduct cytosol and rabbit reticulocyte lysate using anti-p60 and anti-hsp70 monoclonal antibodies confirm that there is a relatively abundant complex in these extracts containing hsp90, hsp70, and p60. This complex appears to comprise an important functional unit in the assembly of progesterone receptor complexes.However, judging from the abundance and widespread occurrence of this multiprotein complex, hsp90, hsp70, and p60 probably function interactively in other systems as well.Numerous recent studies (2,7,8,10,34,49,54) have shown that one of the major heat shock proteins, hsp70, functions in an ATP-dependent manner through transient interactions to mediate folding or unfolding of polypeptide chains. Another major heat shock protein, hsp90, is thought to perhaps also function in some capacity related to folding or protein-protein interactions, but its function(s) remains poorly defined (1). Supporting its potential role in protein folding is a recent demonstration that hsp90 enhances renaturation of some proteins in vitro (52). Perhaps the most widely studied interaction of hsp90 is its identity as a stable component of several unactivated steroid receptor complexes (6, 38, 41). For glucocorticoid receptors, hsp90 binding to receptor is required to maintain high-affinity ligand binding (3,26,40), but other steroid receptors that have been examined do not show this same dependency on hsp90. In all hsp90-nuclear receptor complexes, ligand-dependent activation of the receptor DNA-binding ability is accompanied by dissociation of hsp90 (14,17,31,43), and it appears likely that one hsp90 function is to repress DNA binding by receptor.Steroid receptor-hsp9O interactions provide a model for understanding hsp90 function, but exploiting this model has been hindered by the inability to reversibly assemble receptor-hsp90 complexes in vitro. This drawback was recently overcome by establishing certain physicochemical conditions that permit the use of rabbit reticulocyte...

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Section: Methodsmentioning

confidence: 75%

“…It has been shown to interact with steroid receptors (6,38,41), with a variety of protein kinases (4,24,25,33), and with actin (18) and tubulin (37). Some evidence exists for its possible function as a protein kinase (9,28), and one report indicates a molecular chaperone activity of hsp90 in protein renaturation in vitro (52).…”

Section: Discussionmentioning

confidence: 99%

Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.

et al. 1993

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“…[27][28][29][30][31][32][33][34][35][36][37][38][39] However our understanding of the role played by phosphorylation of distinct residues in regulating the chaperone function of Hsp90 remains incomplete. A number of serine and threonine phosphorylation sites …”

Section: Swe1mentioning

confidence: 99%

Hsp90 phosphorylation, Wee1 and the cell cycle

Mollapour

Tsutsumi²,

Neckers³

2010

Cell Cycle

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“…At higher concentrations, 8-and 19-kDa fragments accumulated. Among them, the 14-kDa fragment was the most resistant to a wide range of trypsin concentrations (lanes [2][3][4][5][6].…”

Section: Resultsmentioning

confidence: 99%

Interaction between the N-terminal and Middle Regions Is Essential for the in Vivo Function of HSP90 Molecular Chaperone

Matsumoto

Tanaka

Nemoto

et al. 2002

Journal of Biological Chemistry

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) and C-terminal one-third of the middle region were sufficient for the interactions with the N-and C-terminal regions, respectively. Yeast HSC82 that carried point mutations in the middle region causing deficient binding to the N-terminal region could not support the growth of HSP82-depleted cells at an elevated temperature. Taken together, our data show that the N-terminal and middle regions of the HSP90 family protein are structurally divided into two respective subregions. Moreover, the interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 in yeast.The 90-kDa heat shock protein (HSP90) 1 has been demonstrated to be an important molecule, chaperoning a variety of cellular proteins, such as steroid receptors (1-3), protein kinases involved in signal transduction (4 -6), and even retrovirus reverse transcriptase (7) and endothelial nitric-oxide synthase (8) (for reviews, see Refs. 9 and 10). HSP90 occupies a central part of the chaperone network, the "foldsome," and functions in cooperation with other chaperones and co-chaperones, such as immunophilins, CDC37/p50, HSP70, p23, Hip, Hop/p60, and PA28 (11-13) (for reviews, see Refs. 9 and 10).This assembly process of the HSP90-substrate protein complex requires ATP (14, 15), which induces a conformational change in HSP90 (16 -18). Recently, it was demonstrated that HSP90 is capable of linking substrates for degradation by the ubiquitin-proteasome pathway by cooperating with the E3 ligase carboxyl terminus of HSC70-interacting protein (CHIP) (19 -21). Thus, HSP90 may play a central role in deciding the fate of proteins, refolding or degradation.HSP90 family proteins are composed of three regions at the primary structure level (22,23). In the present study using human HSP90␣, we denote the N-terminal region, Region B and Region C mediate dimerization of the HSP90 family proteins; Region B of one subunit is associated with Region C of another subunit in an antiparallel fashion (22). Electron microscopy showed that an HSP90 dimer consists of four linearly arranged globules (18), and the N-and C-terminal immunogenic sites (23) were localized in the terminal and interior globules, respectively (28).To accomplish the molecular function of HSP90, each region may have additional roles that should be unveiled. For instance, although the ATP binding site has been localized toward the amino terminus of HSP90, ATP binding as well as elevated temperature bring about a profound conformational change that is not restricted to the ATP-binding domain (16 -18). When the concentration of HSP90 was lower than 1 M, both ATP binding and elevated temperature induced an equivalent conformational change, converting HSP90 from a linear dimer into an O-ring-shaped structure (18). On the other hand, when the concentration of HSP90 was sufficiently high, HSP90 self-oligomerized instead of formed O-ring-shaped molecules, probably through essentially identical interactions (29). Alteration of the regional interaction may be closely related to these ...

show abstract

The 90-kilodalton peptide of the heme-regulated eIF-2.alpha. kinase has sequence homology with the 90-kilodalton heat shock protein

Cited by 129 publications

References 35 publications

Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.

Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.

Hsp90 phosphorylation, Wee1 and the cell cycle

Interaction between the N-terminal and Middle Regions Is Essential for the in Vivo Function of HSP90 Molecular Chaperone

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