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
More filters
Journal ArticleDOI
Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell
TL;DR: This work has reviewed data from the literature and re-analyzed my own studies to describe and discuss these fascinating changes in HspB1 structural organization.
Journal ArticleDOI
Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus.
Luke Whitesell,Nicole Robbins,David S. Huang,Catherine A. McLellan,Tanvi Shekhar-Guturja,Emmanuelle V. LeBlanc,Catherine S. Nation,Raymond Hui,Ashley Hutchinson,Cathy Collins,Sharanya Chatterjee,Richard Trilles,Jinglin L. Xie,Damian J. Krysan,Susan Lindquist,John A. Porco,Utpal Tatu,Lauren E. Brown,Juan C. Pizarro,Leah E. Cowen +19 more
TL;DR: The authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.
Journal ArticleDOI
The network interaction of the human cytosolic 90 kDa heat shock protein Hsp90: A target for cancer therapeutics
TL;DR: The major chaperones and co-chaperones that interact with cytosolic Hsp90s are reviewed, highlighting the latest findings regarding client proteins and the role that posttranslational modifications have on the function and interactions of these molecular chaperone.
Journal ArticleDOI
Label-free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5.
Danalea V. Skarra,Marilyn Goudreault,Hyungwon Choi,Michael Mullin,Alexey I. Nesvizhskii,Anne-Claude Gingras,Anne-Claude Gingras,Richard E. Honkanen,Richard E. Honkanen +8 more
TL;DR: The results presented demonstrate the usefulness of label‐free quantitative proteomics and statistical tools to discriminate between noise and true interactions, even for proteins normally considered as background contaminants.
Journal ArticleDOI
Opposing Actions of Heat Shock Protein 90 and 70 Regulate Nicotinamide Adenine Dinucleotide Phosphate Oxidase Stability and Reactive Oxygen Species Production
Feng Chen,Yanfang Yu,Jin Qian,Yusi Wang,Bo Cheng,Christiana Dimitropoulou,Vijay Patel,Ahmed Chadli,R. Dan Rudic,David W. Stepp,John D. Catravas,David Fulton +11 more
TL;DR: It is concluded that Hsp90 binds to and regulates Nox protein stability, which is opposed by Hsp70 and CHIP, which promote the ubiquitination and degradation of Nox proteins and reduce reactive oxygen species production.
References
More filters
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.