Inhibition of Hsp90: A new strategy for inhibiting protein kinases

Amere Subbarao Sreedhar, Csaba Soti, Péter Csermely

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The 90-kDa heat shock protein (Hsp90) is a ubiquitous, evolutionarily highly conserved, molecular chaperone in the eukaryotic cytosol. Hsp90, together with a number of other chaperones, promotes the conformational maturation of a large variety of protein kinases. Inhibition of Hsp90 function results in the collapse of the metastable conformation of most of these kinases and leads to their proteolytic elimination by the proteasome. Numerous natural and synthetic Hsp90 inhibitors have been developed in recent years. Some of these inhibitors are also involved in sensitizing tumor cells to pro-apoptotic insults, hence serve as anti-cancer drugs. Here we review these novel protein kinase inhibitors and their emerging role in various cellular processes, apart from their inhibition of Hsp90 protein function. We focus not only on Hsp90-tumor progression, but also on cytoarchitecture, as the higher levels of cellular organization need constant remodeling, where the role of Hsp90 requires investigation. Our last major aspect deals with protein oxidation, since several Hsp90 inhibitors exert pro-oxidant effects.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1697
Issue number1-2
DOIs
Publication statusPublished - Mar 11 2004

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Keywords

  • 17-allylamino-17-demethoxy-geldanamycin
  • 17AAG
  • CK II
  • CK refers to the old name of protein kinase CK II, casein kinase
  • Cdk
  • Chaperone
  • Cisplatin
  • Cyclin-dependent kinase
  • EGF
  • Geldanamycin
  • Heat shock protein
  • Hsp90
  • Protein kinase inhibitor

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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