Hsp 90 is critical for cell survival and appears to be important for the maturation of a set of proteins, notably certain transcription factors and kinases. The determination of the range of proteins that it interacts with as well as the means by which it assists proteins to mature are the primary objectives of this study. The extent of interaction with newly synthesized proteins (proteins in the process of maturation) will be determined in whole cell lysates as well as fractionated polysomes. In order to follow the interactive process of hsp 90, in vitro translation of a known substrate, the androgen receptor, will be focused on using both the wild type protein as well as a mutant form of the receptor involved in disease. Here we plan to exploit the fact that the AR represents a co-called 'glutamine expansion' protein associated with neurological disease (ie. spinal/bulbar muscular atrophy). A number of neurodegenerative disease (the best known being Huntingtons disease) are known to arise due to expanded CAG trinucleotide repeats that encode runs of glutamine residues. We anticipate these studies will provide new insights on the still unresolved function of hsp90. In addition we believe the second part of our studies will help us begin to understand the possible connection between molecular chaperones and the pathway by which glutamine expansion proteins undergo misfolding, aggregation and/or degradation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM020572-01
Application #
6139994
Study Section
Special Emphasis Panel (ZRG1-BIO (01))
Program Officer
Ikeda, Richard A
Project Start
2000-06-01
Project End
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
1
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
University of California San Francisco
Department
Surgery
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143