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Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function

Mollapour, Mehdi, Tsutsumi, Shinji, Donnelly, Alison C., Beebe, Kristin, Tokita, Mari J., Lee, Min-Jung, Lee, Sunmin, Morra, Giulia, Bourboulia, Dimitra, Scroggins, Bradley T., and others. (2010) Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function. Molecular Cell, 37 (3). pp. 333-343. ISSN 1097-2765. (doi:10.1016/j.molcel.2010.01.005) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.molcel.2010.01.005

Abstract

Saccharomyces WEE1 (Swe1), the only “true” tyrosine kinase in budding yeast, is an Hsp90 client protein. Here we show that Swe1Wee1 phosphorylates a conserved tyrosine residue (Y24 in yeast Hsp90 and Y38 in human Hsp90?) in the N domain of Hsp90. Phosphorylation is cell-cycle associated and modulates the ability of Hsp90 to chaperone a selected clientele, including v-Src and several other kinases. Nonphosphorylatable mutants have normal ATPase activity, support yeast viability, and productively chaperone the Hsp90 client glucocorticoid receptor. Deletion of SWE1 in yeast increases Hsp90 binding to its inhibitor geldanamycin, and pharmacologic inhibition/silencing of Wee1 sensitizes cancer cells to Hsp90 inhibitor-induced apoptosis. These findings demonstrate that Hsp90 chaperoning of distinct client proteins is differentially regulated by specific posttranslational modification of a unique subcellular pool of the chaperone, and they provide a strategy to increase the cellular potency of Hsp90 inhibitors.

Item Type: Article
DOI/Identification number: 10.1016/j.molcel.2010.01.005
Additional information: number of additional authors: 18;
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 29 May 2019 12:23 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40378 (The current URI for this page, for reference purposes)
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