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.
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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
Structural Analysis of E. coli hsp90 Reveals Dramatic Nucleotide-Dependent Conformational Rearrangements
TL;DR: The effects of nucleotides on the structure of full-length HtpG, the Escherichia coli hsp90 ortholog, are described, suggesting a mechanism by which nucleotide could control client protein binding and release.
Journal ArticleDOI
Heat-shock protein hsp90 governs the activity of pp60v-src kinase
Yang Xu,Susan Lindquist +1 more
TL;DR: It is concluded that hsp90 does not simply suppress pp60v-src kinase activity during transit to the plasma membrane, but also stabilizes the protein and affects both its activity and specificity.
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Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu
TL;DR: It is shown that the chaperone-binding ubiquitin ligase CHIP efficiently ubiquitinates and down-regulates ErbB2, and a previously unrecognized pathway, amenable to pharmacologic manipulation, that mediates Erb B2 stability is described.
Journal ArticleDOI
A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses
TL;DR: It is shown that many NLRs interacted with the ubiquitin ligase–associated protein SGT1 and heat-shock protein 90, both of which have plant orthologs essential for R-protein responses.
Journal ArticleDOI
An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function
Bradley T. Scroggins,Kenneth Robzyk,Dongxia Wang,Monica G. Marcu,Shinji Tsutsumi,Kristin Beebe,Robert J. Cotter,Sara J. Felts,David O. Toft,Larry M. Karnitz,Neal Rosen,Len Neckers +11 more
TL;DR: It is demonstrated that Hsp90 K294 is acetylated and Mutational analysis of K294 shows that its acetylation status is a strong determinant of client protein and cochaperone binding, suggesting that acetylations/deacetylation of K 294 plays an important role in regulating the Hsp 90 chaperone cycle.