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
Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.
David F. Smith,William P. Sullivan,Tony N. Marion,Kiyoshi Zaitsu,Benjamin Madden,Daniel J. McCormick,David O. Toft +6 more
TL;DR: Immunoaffinity purification of hsp90 from chick oviduct cytosol reveals two major proteins, hsp70 and a 60-kDa protein (p60), copurifying with hsp 90, which appears to comprise an important functional unit in the assembly of progesterone receptor complexes.
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Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37.
Giuliano Siligardi,Barry Panaretou,Philippe Meyer,Shradha Singh,Derek N. Woolfson,Peter W. Piper,Laurence H. Pearl,Chrisostomos Prodromou +7 more
TL;DR: It is shown that Cdc37p/p50 cdc37, like Sti1/Hop/p60, also suppresses ATP turnover by Hsp90 supporting the idea that client protein loading to HSp90 requires a “relaxed” ADP-bound conformation.
Journal ArticleDOI
Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons
Valeria Specchia,Lucia Piacentini,Patrizia Tritto,Laura Fanti,Rosalba D’Alessandro,G. Palumbo,Sergio Pimpinelli,Maria Pia Bozzetti +7 more
TL;DR: It is shown that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants, which indicates that Hsp 90 mutations can generate new variation by transposOn-mediated ‘canonical’ mutagenesis.
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Protein Phosphatase 5 Is a Major Component of Glucocorticoid Receptor·hsp90 Complexes with Properties of an FK506-binding Immunophilin
Adam M. Silverstein,Mario D. Galigniana,Mei-Shya Chen,Janet K. Owens-Grillo,Michael Chinkers,William B. Pratt +5 more
TL;DR: It is proposed that PP5 possesses properties of an immunophilin with low affinity FK506 binding activity and that it determines a major portion of the native GR heterocomplexes in L cell cytosol.
Journal ArticleDOI
Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways.
TL;DR: The finding that a distinct chaperone complex is uniquely required for quality control provides evidence for active and specific chaperones participation in triage decisions and suggests that a hierarchy of chaper one interactions can control the alternate fates of a cytosolic protein.