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Expressed as the sole Hsp90 of yeast, the α and β isoforms of human Hsp90 differ with regard to their capacities for activation of certain client proteins, whereas only Hsp90β generates sensitivity to the Hsp90 inhibitor radicicol
Author(s) -
Millson Stefan H.,
Truman Andrew W.,
Rácz Attila,
Hu Bin,
Panaretou Barry,
Nuttall James,
Mollapour Mehdi,
Söti Csaba,
Piper Peter W.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05974.x
Subject(s) - hsp90 , heat shock protein , biology , gene isoform , microbiology and biotechnology , hsp90 inhibitor , yeast , extracellular , cytosol , protein kinase a , kinase , transcription factor , biochemistry , gene , enzyme
Heat shock protein 90 (Hsp90) is a molecular chaperone required for the activity of many of the most important regulatory proteins of eukaryotic cells (the Hsp90 ‘clients’). Vertebrates have two isoforms of cytosolic Hsp90, Hsp90α and Hsp90β. Hsp90β is expressed constitutively to a high level in most tissues and is generally more abundant than Hsp90α, whereas Hsp90α is stress‐inducible and overexpressed in many cancerous cells. Expressed as the sole Hsp90 of yeast, human Hsp90α and Hsp90β are both able to provide essential Hsp90 functions. Activations of certain Hsp90 clients (heat shock transcription factor, v‐src) were more efficient with Hsp90α, rather than Hsp90β, present in the yeast. In contrast, activation of certain other clients (glucocorticoid receptor; extracellular signal‐regulated kinase‐5 mitogen‐activated protein kinase) was less affected by the human Hsp90 isoform present in these cells. Remarkably, whereas expression of Hsp90β as the sole Hsp90 of yeast rendered cells highly sensitive to the Hsp90 inhibitor radicicol, comparable expression of Hsp90α did not. This raises the distinct possibility that, also for mammalian systems, alterations to the Hsp90α/Hsp90β ratio (as with heat shock) might be a significant factor affecting cellular susceptibility to Hsp90 inhibitors.