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Permanent link (DOI): https://doi.org/10.7939/R3VD5N

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Characterization of the motif requirements for the function of Aha1p and its homologue Hch1p Open Access

Descriptions

Other title
Subject/Keyword
ATPase
Hch1
Hsp90
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Horvat, Natalie K
Supervisor and department
LaPointe, Paul (Cell Biology)
Examining committee member and department
Hughes, Sarah (Cell Biology)
Simmen, Thomas (Cell Biology)
Underhill, Alan (Oncology)
Department
Department of Cell Biology
Specialization

Date accepted
2013-09-25T11:53:25Z
Graduation date
2013-11
Degree
Master of Science
Degree level
Master's
Abstract
The Hsp90 chaperone facilitates the maturation of client proteins, which are key players in cancer. Hsp90 inhibitor drugs, such as NVP-AUY922, are promising anti-cancer therapies. Co-chaperones regulate the ATPase-dependent Hsp90 activity and specifically, the co-chaperone Aha1 is the most robust stimulator of Hsp90 ATPase activity. Hch1p is a homologue of Aha1p and shares numerous conserved motifs. The conserved RKxK motif is involved in remodeling of the catalytic loop in Hsp90 and is required for Hch1p and Aha1p function. Surprisingly, the highly conserved N terminal peptide NxxNWHW is required for Hch1p activity in vivo but not for ATPase stimulation by either co-chaperone in vitro. Interestingly, Hch1p regulates sensitivity to Hsp90 inhibitor drugs in vivo whereas Aha1p does not. I propose that Hch1p regulates a step distinct than that of Aha1p which occurs early in the Hsp90 cycle and is sensitive to drug inhibition.
Language
English
DOI
doi:10.7939/R3VD5N
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File format: pdf (Portable Document Format)
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File size: 11583133
Last modified: 2015:10:12 11:27:47-06:00
Filename: Horvat_Natalie_Fall2013.pdf
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Status message: File header gives version as 1.4, but catalog dictionary gives version as 1.3
File title: 2013 09 18 THESIS FINAL DRAFT
File author: Katarina Horvat
Page count: 159
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