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
Structure, Function, and Regulation of the Hsp90 Machinery
TL;DR: Recent structural and mechanistic progress in defining the function of organelle-specific and cytosolic Hsp90 is summarized, including the impact of individual cochaperones on the maturation of specific clients and complexes with clients as well as ways of exploiting HSp90 as a drug target.
Journal ArticleDOI
Role of Heat-Shock Proteins in Cellular Function and in the Biology of Fungi.
TL;DR: Role of Hsps in fungi during morphogenesis and various stress conditions (temperature, pH, and osmotic pressure) and in antifungal drug tolerance is focused on.
Journal ArticleDOI
Targeted therapies for treatment of non-small cell lung cancer--Recent advances and future perspectives.
TL;DR: The development of targeted therapies for the treatment of advanced or metastatic NSCLC are reviewed, including those already in clinical practice and those in early trials, including the immune checkpoint inhibitor nivolumab.
Journal ArticleDOI
Substrate binding drives large-scale conformational changes in the Hsp90 molecular chaperone.
TL;DR: The results suggest that Hsp90 preferentially binds a locally structured region in a globally unfolded protein, and this binding drives functional changes in the chaperone by lowering a rate-limiting conformational barrier.
Journal ArticleDOI
Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions
TL;DR: Various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders are reviewed.
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
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.
Journal ArticleDOI
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.