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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Inhibitory effects of heat shock protein 90 blockade on proinflammatory human Th1 and Th17 cell subpopulations
TL;DR: The results further support the potential use of Hsp90 inhibitors in patients with autoimmune diseases where uncontrolled Th1 or Th17 activation frequently occurs and are associated with inhibition of NF-kB activity, upregulation of HSp70 protein expression, and disruption of T cell-specific nonreceptor tyrosine kinase Lck activation.
Journal ArticleDOI
HSP90 and co-chaperones: a multitaskers’ view on plant hormone biology
Martin Di Donato,Markus Geisler +1 more
TL;DR: An overview of the multiple roles of HSP90 and its co‐chaperones in plant hormone biology is given and the largely unexplored targets for signal integration that the activity of these apparent multitaskers may suggest are discussed.
Journal ArticleDOI
HSP90 recognizes the N-terminus of huntingtin involved in regulation of huntingtin aggregation by USP19
TL;DR: Mechanistic insights are provided into the recognition between HSP90 and the N-terminus of Htt, and the triage decision for the Htt protein by the H SP90 chaperone system.
Journal ArticleDOI
HSP70 and HSP90 in neurodegenerative diseases.
TL;DR: Small molecules that inhibit the HSP90 but also increase the H SP70 has been tested as potential drugs for neurodegenerative disorders.
Journal ArticleDOI
Galbanic acid decreases androgen receptor abundance and signaling and induces G1 arrest in prostate cancer cells.
Yong Zhang,Yong Zhang,Yong Zhang,Kwan Hyun Kim,Kwan Hyun Kim,Wei Zhang,Yinglu Guo,Sung Hoon Kim,Junxuan Lu +8 more
TL;DR: The observations of anti‐AR and cell cycle arrest actions plus the anti‐angiogenesis effect reported elsewhere suggest GBA as a multitargeting drug candidate for the prevention and therapy of PCa.
References
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Journal ArticleDOI
Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
Paul T C Wan,Mathew J. Garnett,S. Mark Roe,Sharlene Lee,Dan Niculescu-Duvaz,Valerie M. Good,Cancer Genome,C. Michael Jones,Christopher J. Marshall,Caroline J. Springer,David Barford,Richard Marais +11 more
TL;DR: The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism.
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HSP90 and the chaperoning of cancer.
TL;DR: Pharmacologically 'bribing' the essential guard duty of the chaperone HSP90 (heat-shock protein of 90 kDa) seems to offer a unique anticancer strategy of considerable promise.
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Hsp90 as a capacitor for morphological evolution
TL;DR: It is reported that when Drosophila Hsp90 is mutant or pharmacologically impaired, phenotypic variation affecting nearly any adult structure is produced, with specific variants depending on the genetic background and occurring both in laboratory strains and in wild populations.
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Adapting proteostasis for disease intervention.
TL;DR: The proteostasis network is described, a set of interacting activities that maintain the health of proteome and the organism that has the potential to ameliorate some of the most challenging diseases of this era.
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Function and regulation of cullin-RING ubiquitin ligases.
TL;DR: This review focuses on the composition, regulation and function of cullin–RING ligases, and describes how these enzymes can be characterized by a set of general principles.