Our recent work showed that the maintenance of open chromatin is dependent upon the p23 molecular chaperone.

Homeostasis relies on a pliable chromatin structure to effectively and promptly execute DNA- associated activities including gene regulation and chromosome preservation. 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. In brief, we are investigating the individual and joint regulatory effects of Hsp90 and p23 on nucleosome remodeling process. To achieve our goal we are exploiting chromatin remodelers as molecular models. Proteostasis is achieved by an integrated network of several hundred proteins 4, including, most prominently, molecular chaperones and their regulators, which assist in de novo folding or. Our current plans will resolve how molecular chaperones cooperatively modulate multi-subunit protein complexes. We will exploit our discoveries connecting the Hsp90 system to chromatin modifiers to determine why certain chaperones interact with select native proteins. The significance of chaperone interactions with seemingly native proteins is poorly understood.

Yet, chaperones in the Hsp90 system are often associated with native proteins including assembled structures. Molecular chaperones are typically identified with the beginning (folding) and ending (degradation) of the protein life cycle. Our long-term objectives are to understand the Hsp90 molecular chaperone system from physiological relevance to mechanistic action.

Molecular chaperone systems