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Mol. Cell. Biol. May (2008); 28(10):3446-56
p23-Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity-
Forafonov F, Toogun OA, Grad I, Suslova E, Freeman BC, Picard D
Departement de Biologie Cellulaire, Universite de Geneve, Sciences III, CH-1211 Geneve 4, Switzerland-
Abstract: The molecular chaperone Hsp90 assists a subset of cellular proteins and is essential in eukaryotes- A cohort of cochaperones contributes to and regulates the multicomponent Hsp90 machine- Unlike the biochemical activities of the cochaperone p23, its in vivo functions and the structure-function relationship remain poorly understood, even in the genetically tractable model organism Saccharomyces cerevisiae- The SBA1 gene that encodes the p23 ortholog in this species is not an essential gene- We found that in the absence of p23-Sba1p, yeast and mammalian cells are hypersensitive to Hsp90 inhibitors- This protective function of Sba1p depends on its abilities to bind Hsp90 and to block the Hsp90 ATPase and inhibitor binding- In contrast, the protective function of Sba1p does not require the Hsp90-independent molecular chaperone activity of Sba1p- The structure-function analysis suggests that Sba1p undergoes considerable structural rearrangements upon binding Hsp90 and that the large size of the p23-Sba1p-Hsp90 interaction surface facilitates maintenance of high affinity despite sequence divergence during evolution- The large interface may also contribute to preserving a protective function in an environment in which Hsp90 inhibitory compounds can be produced by various microorganisms-
[PUBMED: 18362168] Download Biogrid Interactions in a variety of formats including PSI FormatPUBMED
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.