An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function

Bradley T. Scroggins, Kenneth Robzyk, Dongxia Wang, Monica G. Marcu, Shinji Tsutsumi, Kristin Beebe, Robert J. Cotter, Sara Felts, David Toft, Larry M Karnitz, Neal Rosen, Len Neckers

Research output: Contribution to journalArticle

272 Citations (Scopus)

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 posttranslational modifications that affect its function, including acetylation. Histone deacetylase (HDAC) inhibitors and knockdown 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 WT 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.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalMolecular Cell
Volume25
Issue number1
DOIs
StatePublished - Jan 12 2007

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HSP90 Heat-Shock Proteins
Acetylation
Histone Deacetylase Inhibitors
Post Translational Protein Processing
Protein Binding
Yeasts

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Scroggins, B. T., Robzyk, K., Wang, D., Marcu, M. G., Tsutsumi, S., Beebe, K., ... Neckers, L. (2007). An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function. Molecular Cell, 25(1), 151-159. https://doi.org/10.1016/j.molcel.2006.12.008

An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function. / Scroggins, Bradley T.; Robzyk, Kenneth; Wang, Dongxia; Marcu, Monica G.; Tsutsumi, Shinji; Beebe, Kristin; Cotter, Robert J.; Felts, Sara; Toft, David; Karnitz, Larry M; Rosen, Neal; Neckers, Len.

In: Molecular Cell, Vol. 25, No. 1, 12.01.2007, p. 151-159.

Research output: Contribution to journalArticle

Scroggins, BT, Robzyk, K, Wang, D, Marcu, MG, Tsutsumi, S, Beebe, K, Cotter, RJ, Felts, S, Toft, D, Karnitz, LM, Rosen, N & Neckers, L 2007, 'An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function', Molecular Cell, vol. 25, no. 1, pp. 151-159. https://doi.org/10.1016/j.molcel.2006.12.008
Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K et al. An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function. Molecular Cell. 2007 Jan 12;25(1):151-159. https://doi.org/10.1016/j.molcel.2006.12.008
Scroggins, Bradley T. ; Robzyk, Kenneth ; Wang, Dongxia ; Marcu, Monica G. ; Tsutsumi, Shinji ; Beebe, Kristin ; Cotter, Robert J. ; Felts, Sara ; Toft, David ; Karnitz, Larry M ; Rosen, Neal ; Neckers, Len. / An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function. In: Molecular Cell. 2007 ; Vol. 25, No. 1. pp. 151-159.
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