GCUNC45 is the first Hsp90 Co-chaperone to show α/β isoform specificity

Ahmed Chadli, Sara J. Felts, David O. Toft

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hsp90 is an essential molecular chaperone required for the normal functioning of many key regulatory proteins in eukaryotic cells. Vertebrates have two closely related isoforms of cytosolic Hsp90 (Hsp90α and Hsp90β). However, specific functions for each isoform are largely unknown, and no Hsp90 co-chaperone has been reported to distinguish between the two isoforms. In this study, we show that the Hsp90 co-chaperone GCUNC45 bound preferentially to the β isoform of Hsp90 in vitro. GCUNC45 efficiently blocked the progression of progesterone receptor chaperoning in an in vitro functional system when Hsp90β was used, but did so with much less efficacy when Hsp90α was used. Knockdown experiments in HeLa cells showed that GCUNC45 is required for the normal cellular distribution of Hsp90β, but not Hsp90α. This is the first example of a co-chaperone with isoform selectivity, and this approach may open novel avenues to understanding the functional differences between Hsp90 isoforms.

Original languageEnglish (US)
Pages (from-to)9509-9512
Number of pages4
JournalJournal of Biological Chemistry
Volume283
Issue number15
DOIs
StatePublished - Apr 11 2008

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Protein Isoforms
Molecular Chaperones
Normal Distribution
Eukaryotic Cells
Progesterone Receptors
HeLa Cells
Vertebrates
Proteins
Experiments
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

GCUNC45 is the first Hsp90 Co-chaperone to show α/β isoform specificity. / Chadli, Ahmed; Felts, Sara J.; Toft, David O.

In: Journal of Biological Chemistry, Vol. 283, No. 15, 11.04.2008, p. 9509-9512.

Research output: Contribution to journalArticle

Chadli, Ahmed ; Felts, Sara J. ; Toft, David O. / GCUNC45 is the first Hsp90 Co-chaperone to show α/β isoform specificity. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 15. pp. 9509-9512.
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