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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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.
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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
Comparative genomics and evolution of the HSP90 family of genes across all kingdoms of organisms
TL;DR: The present study presents the first comparative genomic study and evolutionary analysis of the HSP90 family of genes across all kingdoms of organisms, and established an overall framework of information for thefamily of genes which may facilitate and stimulate the study of this gene family across all organisms.
Journal ArticleDOI
A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src.
S M Schuh,W Yonemoto,Joan S. Brugge,Vickie J. Bauer,Robert M. Riehl,William P. Sullivan,David O. Toft +6 more
TL;DR: These present studies implicate a new role for this 90-kDa protein in the action of steroid hormones, which is indistinguishable from one of the major heat shock proteins which are induced under a variety of stress conditions in eukaryotic cells.
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Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones.
TL;DR: A crystal structure of mammalian GRP94 in complex with AMPPNP and ADP is reported and a model for the role of ATP binding and hydrolysis in theGRP94 chaperone cycle is suggested.
Journal ArticleDOI
Protein quality control: chaperones culling corrupt conformations.
TL;DR: The importance of defining the mechanisms and factors that mediate cytoplasmic quality control is underscored by the growing list of diseases associated with protein misfolding and aggregation as mentioned in this paper.
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A protein-folding reaction under kinetic control
TL;DR: By omitting the pro region in an in vitrorefolding reaction, an inactive, but folding competent state (I) having an expanded radius yet native-like secondary structure is trapped, stable for weeks at physiological pH in the absence of denaturant.