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
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Enhanced in vivo antitumor efficacy of dual-functional peptide-modified docetaxel nanoparticles through tumor targeting and Hsp90 inhibition.
Yao Jiang,Nan Yang,Huifeng Zhang,Bo Sun,Chunying Hou,Chao Ji,Ji Zheng,Yanyong Liu,Pingping Zuo +8 more
TL;DR: The feasibility of dual- functional NPs for efficient anticancer therapy is demonstrated by modifying docetaxel nanoparticles (DNP) with the dual-functional ligand LPLTPLP, which exhibited significantly improved antitumor efficacy and biodistribution compared with nontargeting nanodrug and free docetAXel.
Journal ArticleDOI
The regulatory mechanism of a client kinase controlling its own release from Hsp90 chaperone machinery through phosphorylation
TL;DR: This study proves that PKCγ (protein kinase Cγ) is a client protein of Hsp90α, and, that by interacting with PKCα, Hsp 90α prevents PKCβ degradation and facilitates its cytosol-to-membrane translocation and activation, and is the first example to show that a client kinase directly regulates HSp90 activity.
Journal ArticleDOI
Modulation of Molecular Chaperones in Huntington’s Disease and Other Polyglutamine Disorders
TL;DR: A focused review on Hsp90, Hsp70, and their co-chaperones, and how their genetic or pharmacological modulation affects the proteostasis and disease phenotypes in cellular and animal models of polyglutamine disorders suggests different interactions with the cellular protestasis machinery.
Journal ArticleDOI
Interaction of E. coli Hsp90 with DnaK Involves the DnaJ Binding Region of DnaK
TL;DR: The results suggest that a specific region in the NBD of DnaK is involved in the interaction with Hsp90Ec, and this interaction is functionally important.
Journal ArticleDOI
Getting folded: chaperone proteins in muscle development, maintenance and disease.
TL;DR: How chaperone proteins are involved in myofibrillogenesis, sarcomere maintenance, and muscle disorders is discussed and the possibilities of therapeutically targeting chaperones to treat muscle disease are considered.
References
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Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
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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.