Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1.
نویسندگان
چکیده
Client protein activation by Hsp90 involves a plethora of cochaperones whose roles are poorly defined. A ubiquitous family of stress-regulated proteins have been identified (Aha1, activator of Hsp90 ATPase) that bind directly to Hsp90 and are required for the in vivo Hsp90-dependent activation of clients such as v-Src, implicating them as cochaperones of the Hsp90 system. In vitro, Aha1 and its shorter homolog, Hch1, stimulate the inherent ATPase activity of yeast and human Hsp90. The identification of these Hsp90 cochaperone activators adds to the complex roles of cochaperones in regulating the ATPase-coupled conformational changes of the Hsp90 chaperone cycle.
منابع مشابه
Activation of the ATPase Activity of Hsp 90 by the Stress - Regulated Cochaperone
eukaryotic cells (Pearl and Prodromou, 2002). Rather than acting at an early stage of folding, Hsp90 binds client proteins in a substantially folded form and faciliBarry Panaretou,1 Giuliano Siligardi,2 Philippe Meyer,3 Alison Maloney,4 Janis K. Sullivan,1 Shradha Singh,3 Stefan H. Millson,5 Paul A. Clarke,4 tates their association with cofactors or other proteins Soren Naaby-Hansen,5,6 Rob Ste...
متن کاملSilencing of HSP90 cochaperone AHA1 expression decreases client protein activation and increases cellular sensitivity to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin.
AHA1 (activator of HSP90 ATPase) is a cochaperone of the ATP-dependent molecular chaperone, HSP90, which is involved in the maturation, stabilization/degradation, and function of oncogenic proteins. HSP90 operates in a multimeric complex driven by the binding and hydrolysis of ATP. Treatment of cells with the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) results in the degrada...
متن کاملModulation of the cochaperone AHA1 regulates heat-shock protein 90 and endothelial NO synthase activation by vascular endothelial growth factor.
OBJECTIVE Vascular endothelial growth factor (VEGF) signaling to endothelial NO synthase (eNOS) plays a central role in angiogenesis. In endothelial cells (ECs), heat-shock protein 90 (Hsp90) is also a regulator of eNOS activity. Our study is designed to determine whether modulation of the activator of Hsp90 ATPase 1 (AHA1) regulates the function of Hsp90 in ECs. METHODS AND RESULTS We show t...
متن کاملStructural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery.
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متن کاملAha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone.
The ATP-dependent molecular chaperone Hsp90 is an essential and abundant stress protein in the eukaryotic cytosol that cooperates with a cohort of cofactors/cochaperones to fulfill its cellular tasks. We have identified Aha1 (activator of Hsp90 ATPase) and its relative Hch1 (high copy Hsp90 suppressor) as binding partners of Hsp90 in Saccharomyces cerevisiae. By using genetic and biochemical ap...
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ورودعنوان ژورنال:
- Molecular cell
دوره 10 6 شماره
صفحات -
تاریخ انتشار 2002