Cdc37 Interacts with the Glycine-Rich Loop of Hsp90 Client Kinases
نویسندگان
چکیده
منابع مشابه
Hsp90 recognizes a common surface on client kinases.
Hsp90 is a highly abundant chaperone whose clientele includes hundreds of cellular proteins, many of which are central players in key signal transduction pathways and the majority of which are protein kinases. In light of the variety of Hsp90 clientele, the mechanism of selectivity of the chaperone toward its client proteins is a major open question. Focusing on human kinases, we have demonstra...
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Activation of many protein kinases depends on their interaction with the Hsp90 molecular chaperone system. Recruitment of protein kinase clients to the Hsp90 chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts as a scaffold, simultaneously binding protein kinases and Hsp90. We have now expressed and purified an Hsp90-Cdc37-Cdk4 complex, defined its stoichiometry, a...
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HSP90 is a molecular chaperone that associates with numerous substrate proteins called clients. It plays many important roles in human biology and medicine, but determinants of client recognition by HSP90 have remained frustratingly elusive. We systematically and quantitatively surveyed most human kinases, transcription factors, and E3 ligases for interaction with HSP90 and its cochaperone CDC3...
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Hsp90 is a molecular chaperone, a vital protein that facilitates the folding and unfolding of a variety of proteins or ‘clients’. Kinases are one such client, with over half of the human kinome dependent on Hsp90 for activation (1). As its name suggests, Hsp90 is a heat shock protein and thus is highly expressed when the cell is under stress to ensure that proteins are folded and active. Its ex...
متن کاملATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system.
Protein kinase clients are recruited to the Hsp90 molecular chaperone system via Cdc37, which simultaneously binds Hsp90 and kinases and regulates the Hsp90 chaperone cycle. Pharmacological inhibition of Hsp90 in vivo results in degradation of kinase clients, with a therapeutic effect in dependent tumors. We show here that Cdc37 directly antagonizes ATP binding to client kinases, suggesting a r...
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ژورنال
عنوان ژورنال: Molecular and Cellular Biology
سال: 2006
ISSN: 0270-7306,1098-5549
DOI: 10.1128/mcb.26.9.3378-3389.2006