1. An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function
- Author
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Dongxia Wang, Len Neckers, Bradley T. Scroggins, Shinji Tsutsumi, Robert J. Cotter, Sara J. Felts, David O. Toft, Kenneth Robzyk, Kristin Beebe, Larry M. Karnitz, Neal Rosen, and Monica G. Marcu
- Subjects
Lysine ,Molecular Sequence Data ,Plasma protein binding ,Saccharomyces cerevisiae ,SAP30 ,Article ,Mice ,Chlorocebus aethiops ,polycyclic compounds ,Animals ,Humans ,Amino Acid Sequence ,HSP90 Heat-Shock Proteins ,Molecular Biology ,biology ,Acetylation ,Cell Biology ,HDAC6 ,Hsp90 ,Protein Structure, Tertiary ,Biochemistry ,Chaperone (protein) ,COS Cells ,Checkpoint Kinase 1 ,Mutation ,biology.protein ,NIH 3T3 Cells ,Mutant Proteins ,Histone deacetylase ,Protein Kinases ,Protein Binding - Abstract
Heat shock protein 90 (Hsp90) chaperones a key subset of signaling proteins and is necessary for malignant transformation. Hsp90 is subject to an array of post-translational modifications which affect its function, including acetylation. Histone deacetylase (HDAC) inhibitors and knock-down of HDAC6 induce Hsp90 acetylation and inhibit its activity. However, direct determination of the functional consequences of Hsp90 acetylation has awaited mapping of specific sites. We now demonstrate that Hsp90 K294 is acetylated. Mutational analysis of K294 shows that its acetylation status is a strong determinant of client protein and cochaperone binding. In yeast, Hsp90 mutants that cannot be acetylated at K294 have reduced viability and chaperone function compared to wild type or to mutants that mimic constitutive acetylation. These data suggest that acetylation/deacetylation of K294 plays an important role in regulating the Hsp90 chaperone cycle.
- Published
- 2007
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