Hsp90 and p23 Molecular Chaperones Control Chromatin Architecture by Maintaining the Functional Pool of the RSC Chromatin Remodeler.
Molecular chaperones govern protein homeostasis, being allied to the beginning (folding) and ending (degradation) of the protein life cycle. Yet, the Hsp90 system primarily associates with native factors, including fully assembled complexes. The significance of these connections is poorly understood. To delineate why Hsp90 and its cochaperone p23 interact with a mature structure, we focused on the RSC chromatin remodeler. Both Hsp90 and p23 triggered the release of RSC from DNA or a nucleosome. Although Hsp90 only freed bound RSC, p23 enhanced nucleosome remodeling prior to discharging the complex. In vivo, RSC mobility and remodeling function were chaperone dependent. Our results suggest Hsp90 and p23 contribute to proteostasis by chaperoning mature factors through energetically unfavorable events, thereby maintaining the cellular pool of active native proteins. In the case of RSC, p23 and Hsp90 promote a dynamic action, allowing a limited number of remodelers to effectively maintain chromatin in a pliable state.
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
Frank J
FJ
Echtenkamp
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA; Department Chemie, Technische Universität München, Garching 85748, Germany.
Zlata
Z
Gvozdenov
Program of Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Nicholas L
NL
Adkins
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
Yang
Y
Zhang
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
Melinda
M
Lynch-Day
Program of Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Shinya
S
Watanabe
Program of Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Craig L
CL
Peterson
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA. Electronic address: bfree@illinois.edu.
Brian C
BC
Freeman
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D009707:Nucleosomes; C103337:RSC complex, S cerevisiae; C113025:SBA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
Hsp90; RSC; chromatin remodeling; molecular chaperones; p23; protein dynamics