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Investigation of Hsp90 regulation by a conserved N‐terminal motif in the Aha1/Hch1 co‐chaperone family (567.6)
Author(s) -
Mercier Rebecca,
Mann Udaybir,
Wolmarans Annemarie,
Horvat Natalie,
LaPointe Paul
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.567.6
Subject(s) - chaperone (clinical) , hsp90 , biology , co chaperone , microbiology and biotechnology , cdc37 , transcription factor , transcription (linguistics) , saccharomyces cerevisiae , genetics , gene , heat shock protein , medicine , linguistics , philosophy , pathology
The molecular chaperone Hsp90 functions in a complex cycle for the maturation and activation of a diverse, but specific, group of client proteins. These clients range from transcription factors to kinases and many are key players in cancer. Consequently, understanding the cycle through which Hsp90 acts is imperative. Hsp90 has a large cohort of co‐chaperone proteins which regulate cycle progression and facilitate client maturation. The co‐chaperone Aha1p is of particular importance as it is the only known co‐chaperone which is a potent stimulator of Hsp90 ATPase activity. The co‐chaperone Hch1p, found in some fungi, is a homologue of Aha1p but regulates Hsp90 function differently. The N‐terminal motif, NxxNWHW, is conserved across the Aha1p/Hch1p family. We show that this motif is necessary for Hch1p function in vivo but is dispensable for the in vitro activity of Aha1p. Functional assays developed in both the model organism Saccharomyces cerevisiae and in mammalian cells reveal the importance of this N‐terminal motif. Additionally, isolation of Hsp90/co‐chaperone complexes provides clues regarding the Hsp90 functional cycle. We are able to provide further support for the dual role of the Aha1p/Hch1p co‐chaperone family in the regulation of Hsp90 activity, both early and late in the Hsp90 cycle. Grant Funding Source : Supported by CIHR and NSERC