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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Hsp90 structure and function studied by NMR spectroscopy
TL;DR: The different approaches that allowed the investigation of Hsp90 using state-of-the-art NMR methods and the results that were obtained are described and the ability of this method to contribute to the structural characterization of not fully folded proteins becomes crucial.
Journal ArticleDOI
In Vivo Conformational Dynamics of Hsp90 and Its Interactors
TL;DR: A mass-spectrometry-based approach was developed that allowed quantitative measurements of in vitro and in-vivo effects of small-molecule inhibitors on Hsp90 conformation, and interaction with co-chaperones and client proteins, and was able to derive structural models for how HSp90 engages its interaction partners in vivo, and how different drugs affect these structures.
Journal ArticleDOI
Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle
TL;DR: In this article, the protein Hip interacts with chaperone Hsp70 and slows ADP dissociation from HSP70, thus resulting in a delay in substrate release, and the crystal structures of Hip domains alone or in complex with Hsp 70 nucleotide-binding domain, along with biochemical analyses, explain how Hip performs its activities.
Journal ArticleDOI
Heat Stress Modulates Mycelium Growth, Heat Shock Protein Expression, Ganoderic Acid Biosynthesis, and Hyphal Branching of Ganoderma lucidum via Cytosolic Ca2+
Xue Zhang,Ang Ren,Mengjiao Li,Peng-Fei Cao,Tian-Xi Chen,Guang Zhang,Liang Shi,Ai-Liang Jiang,Mingwen Zhao +8 more
TL;DR: This research offers a new way to understand the mechanism underlying the physiological and metabolic responses to other environmental factors in G. lucidum and demonstrates that cytosolic Ca2+ participates in heat shock signal transduction and regulates downstream events in filamentous fungi.
Journal ArticleDOI
How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches.
Kliment A. Verba,David A. Agard +1 more
TL;DR: The surprising results suggest a re-evaluation of the role of chaperones in the kinase lifecycle, and suggest that such interactions potentially allow kinases to more rapidly respond to key signals while simultaneously protecting unstable kinases from degradation and suppressing unwanted basal activity.
References
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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
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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.