Our long-term objectives are to understand the Hsp90 molecular chaperone system from physiological relevance to mechanistic action. Molecular chaperones are typically identified with the beginning (folding) and ending (degradation) of the protein life cycle. Yet, chaperones in the Hsp90 system are often associated with native proteins including assembled structures. The significance of chaperone interactions with seemingly native proteins is poorly understood. We will exploit our discoveries connecting the Hsp90 system to chromatin modifiers to determine why certain chaperones interact with select native proteins. Our current plans will resolve how molecular chaperones cooperatively modulate multi-subunit protein complexes. To achieve our goal we are exploiting chromatin remodelers as molecular models. In brief, we are investigating the individual and joint regulatory effects of Hsp90 and p23 on nucleosome remodeling process. Our plans will define how Hsp90 controls select chromatin remodelers, will identify the joint impact of Hsp90 and p23 on remodelers, will determine the impact of Hsp90 on the chromatin landscape, and will show how the control of chromatin remodelers by Hsp90 and p23 supports homeostasis.

Public Health Relevance

Homeostasis relies on a pliable chromatin structure to effectively and promptly execute DNA- associated activities including gene regulation and chromosome preservation. Our recent work showed that the maintenance of open chromatin is dependent upon the p23 molecular chaperone. Our current plans will determine how Hsp90 contributes independently and in conjunction with p23 to the regulation of select chromatin remodelers in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM118306-09
Application #
9689472
Study Section
Membrane Biology and Protein Processing Study Section (MBPP)
Program Officer
Carter, Anthony D
Project Start
2011-07-12
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2021-04-30
Support Year
9
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820