Expressed as the sole Hsp90 of yeast, the alpha and beta isoforms of human Hsp90 differ with regard to their capacities for activation of certain client proteins, whereas only Hsp90beta generates sensitivity to the Hsp90 inhibitor radicicol

Stefan H. Millson, Andrew W. Truman, Attila Rácz, Bin Hu, Barry Panaretou, James Nuttall, Mehdi Mollapour, Csaba Söti, Peter W. Piper

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)4453-4463
JournalFEBS Journal
Volume274
Issue number17
DOIs
Publication statusPublished - 6 Aug 2007

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