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.
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
The BioGRID Interaction Database
Michael S. Livstone,Bobby-Joe Breitkreutz,Chris Stark,Lorrie Boucher,Andrew Chatr-aryamontri,Rose Oughtred,Julie Nixon,Teresa Reguly,Jennifer M. Rust,Andrew G. Winter,Kara Dolinski,Mike Tyers +11 more
TL;DR: The BioGRID 3.0 web interface contains new search and display features that enable rapid queries across multiple data types and sources that are relevant to human health and is supported by NIH NCRR grant R01 RR024031 to MT and KD.
Journal ArticleDOI
The Nucleation and Maintenance of Heterochromatin by a Histone Deacetylase in Fission Yeast
TL;DR: It is shown that Clr3, a fission yeast homolog of mammalian class II HDACs, acts in a distinct pathway parallel to RNAi-directed heterochromatin nucleation to recruit Clr4 and mediate H3K9 methylation at the silent mating-type region and centromeres and that it limits RNA polymerase II accessibility to naturally silenced repeats at heterochromaatin domains.
Journal ArticleDOI
Purification and characterization of a heat-shock element binding protein from yeast.
Peter K. Sorger,Hugh R.B. Pelham +1 more
TL;DR: The relative affinities of the protein for a range of variant HSE sequences correlates with the ability of these sequences to support heat‐inducible transcription in vivo, suggesting that this polypeptide is involved in the activation of heat‐shock promoters.
Journal ArticleDOI
The small heat shock proteins and their clients
Hitoshi Nakamoto,László Vígh +1 more
TL;DR: The amphitropic small heat shock proteins were shown to associate with membranes, although they do not contain transmembrane domains or signal sequences, and thereby potentially contribute to the maintenance of membrane integrity especially under stress conditions.
Journal ArticleDOI
S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities.
Antonio Martínez-Ruiz,Laura Villanueva,Cecilia González de Orduña,Daniel Lopez-Ferrer,María Ángeles Higueras,Carlos Tarin,Ignacio Rodríguez-Crespo,Jesús Vázquez,Santiago Lamas +8 more
TL;DR: It is suggested that S-nitrosylation may functionally regulate the general activities of Hsp90 and provide a feedback mechanism for limiting eNOS activation.