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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Book Series
Signaling and Communication in Plants.
TL;DR: This chapter ventures to give a survey on the role of auxin as a coordinative signal that regulates patterning of cell differentiation, cell division and cell expansion in the totipotent plant cells.
Journal ArticleDOI
The fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens
TL;DR: Targeting the molecular chaperone Hsp90 has emerged as a promising approach to cripple fungal pathogens, thereby enhancing antifungal efficacy, impairing the evolution of drug resistance, and rendering resistant pathogens responsive to treatment.
Journal ArticleDOI
Molecular analysis of common wheat genes encoding three types of cytosolic heat shock protein 90 (Hsp90): functional involvement of cytosolic Hsp90s in the control of wheat seedling growth and disease resistance
Guan-Feng Wang,X. Wei,Fan Renchun,Huanbin Zhou,Xianping Wang,Chunmei Yu,Lingli Dong,Zhenying Dong,Xiaojie Wang,Zhensheng Kang,Hong-Qing Ling,Qian-Hua Shen,Daowen Wang,Xiangqi Zhang +13 more
TL;DR: This work represents the first systematic determination of wheat genes encoding cytosolic Hsp90s, and provides useful evidence for the functional involvement of cytosols in the control of seedling growth and disease resistance in common wheat.
Journal ArticleDOI
Natural Product Inspired N-Terminal Hsp90 Inhibitors: From Bench to Bedside?
TL;DR: The development of natural product analogs, as well as the development of clinically important inhibitors that arose from natural products that have entered clinical trials are highlighted.
Journal ArticleDOI
Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target
TL;DR: In this paper, a review discusses direct mutp53 protein-targeting drug strategies that are currently being developed at various preclinical levels, focusing on the oncogenic gain-of-function (GOF) missense mutant p53 proteins.
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.