Journal ArticleDOI
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
TLDR
Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions.Abstract:
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that facilitates the maturation of a wide range of proteins (known as clients). Clients are enriched in signal transducers, including kinases and transcription factors. Therefore, HSP90 regulates diverse cellular functions and exerts marked effects on normal biology, disease and evolutionary processes. Recent structural and functional analyses have provided new insights on the transcriptional and biochemical regulation of HSP90 and the structural dynamics it uses to act on a diverse client repertoire. Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions.read more
Citations
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Journal ArticleDOI
Molecular chaperones in protein folding and proteostasis
TL;DR: It is suggested that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease, which may spring from a detailed understanding of the pathways underlying proteome maintenance.
Journal ArticleDOI
The Heat Shock Response: Life on the Verge of Death
TL;DR: This Review summarizes the concepts of the protective Hsp network, and the most conserved Hsps are molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures.
Journal ArticleDOI
Combining immunotherapy and targeted therapies in cancer treatment
TL;DR: Targeted therapies and cytotoxic agents also modulate immune responses, which raises the possibility that these treatment strategies might be effectively combined with immunotherapy to improve clinical outcomes.
Journal ArticleDOI
Molecular Chaperone Functions in Protein Folding and Proteostasis
TL;DR: This review focuses on recent advances in understanding the mechanisms of chaperone action in promoting and regulating protein folding and on the pathological consequences of protein misfolding and aggregation.
Journal ArticleDOI
In vivo aspects of protein folding and quality control
TL;DR: A new view of protein folding is emerging, whereby the energy landscapes that proteins navigate during folding in vivo may differ substantially from those observed during refolding in vitro.
References
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Journal ArticleDOI
Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1.
Barry Panaretou,Giuliano Siligardi,Philippe Meyer,Alison Maloney,Janis K. Sullivan,Shradha Singh,Stefan H. Millson,Paul A. Clarke,Soren Naaby-Hansen,Soren Naaby-Hansen,Robert Stein,Robert Stein,Rainer Cramer,Rainer Cramer,Mehdi Mollapour,Paul Workman,Peter W. Piper,Laurence H. Pearl,Chrisostomos Prodromou +18 more
TL;DR: A ubiquitous family of stress-regulated proteins have been identified (Aha1, activator of Hsp90 ATPase) that bind directly to HSp90 and are required for the in vivo Hsp 90-dependent activation of clients such as v-Src, implicating them as cochaperones of the Hsp80 system.
Journal ArticleDOI
The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of the N-terminal domains
Chrisostomos Prodromou,Barry Panaretou,Barry Panaretou,Shahzad Chohan,Giuliano Siligardi,Ronan O'Brien,John E. Ladbury,S. Mark Roe,Peter W. Piper,Laurence H. Pearl +9 more
TL;DR: Data show that Hsp90 has a molecular ‘clamp’ mechanism, similar to DNA gyrase and MutL, whose opening and closing by transient N‐terminal dimerization are directly coupled to the ATPase cycle.
Journal ArticleDOI
HSP90 interacts with RAR1 and SGT1 and is essential for RPS2-mediated disease resistance in Arabidopsis
TL;DR: It is proposed that RAR1 and SGT1 function closely with HSP90 in chaperoning roles that are essential for disease resistance.
Journal ArticleDOI
Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches.
TL;DR: Several unanticipated functions of Hsp90 under normal conditions and in response to stress are identified, highlighting the potential of the integrated global approach to uncover chaperone functions in the cell.
Journal ArticleDOI
Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein.
TL;DR: It is shown that the 90-kDa receptor-associated phosphoprotein is an abundant cytosolic protein that reacts with a monoclonal antibody that recognizes the 90 -kDa phosphop protein that binds steroid receptors in the chicken oviduct.