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.
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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.
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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
Interaction of Hsp70 chaperones with substrates
TL;DR: Determination of the structure of the substrate binding domain of the Escherichia coli Hsp70 chaperone, DnaK, and the biochemical characterisation of the motif it recognizes within substrates provide insights into the principles governing H Sp70 interaction with polypeptide chains.
Journal ArticleDOI
The glucocorticoid responses are shaped by molecular chaperones.
Iwona Grad,Didier Picard +1 more
TL;DR: The contributions of these molecular chaperones to folding, activation, intracellular transport, transcriptional regulation, and decay of the glucocorticoid receptor are discussed.
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Evidence for an Epigenetic Mechanism by which Hsp90 Acts as a Capacitor for Morphological Evolution
TL;DR: Hsp90 acts as a capacitor for morphological evolution through epigenetic and genetic mechanisms, whereby reduced activity of Hsp90 induces a heritably altered chromatin state.
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In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone
TL;DR: The data suggest that Hsp90 is not required for the de novo folding of most proteins, but it is required for a specific subset of proteins that have greater difficulty reaching their native conformations.
Journal ArticleDOI
Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies
Alice Yam,Alice Yam,Yu Xia,Yu Xia,Hen-Tzu Jill Lin,Alma L. Burlingame,Mark Gerstein,Judith Frydman +7 more
TL;DR: It is demonstrated that the eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaper onin containing TCP1) has broad binding specificity in vitro, similar to the prokaryotic Chaperon in GroEL.