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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Is combination therapy the next step to overcome resistance and reduce toxicities in melanoma
C.M. Nijenhuis,John B. A. G. Haanen,Jan H.M. Schellens,Jan H.M. Schellens,Jos H. Beijnen,Jos H. Beijnen +5 more
TL;DR: The knowledge of the mechanisms involved in intrinsic and acquired resistance to mutated BRAF is increasing swiftly and the elucidation of these mechanisms resulted in the development of rational combination therapies to overcome toxicity and resistance.
Journal ArticleDOI
Molecular docking and pharmacophore studies of heterocyclic compounds as Heat shock protein 90 (Hsp90) Inhibitors.
TL;DR: The analyzed structure pharmacophore results are in consistence with the docking results indicating that both these compounds show antagonistic activity towards HSP90 respectively, and the compounds Q1G and T21 showed better binding affinity.
Journal ArticleDOI
ATM is the primary kinase responsible for phosphorylation of Hsp90α after ionizing radiation
Ameer L. Elaimy,Aarif Ahsan,Katherine Marsh,William B. Pratt,Dipankar Ray,Theodore S. Lawrence,Mukesh K. Nyati +6 more
TL;DR: Evidence is provided that Hsp90α is a component of the signal transduction events mediated by ATM following IR, and that HSp90α loss decreases γH2AX levels, which supports additional investigation into Hsp 90α T5/7 phosphorylation with the goal of developing targeted radiosensitizing therapies.
Journal ArticleDOI
Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila
Xiaolu Zhao,Xiaolu Zhao,Yuan Li,Lili Duan,Xiao Chen,Fengbiao Mao,Mina Juma,Yifan Liu,Weibo Song,Shan Gao +9 more
TL;DR: This work studied SMYD1, the only homologue of SMYD in the unicellular eukaryote Tetrahymena thermophila, and analyzed its localization and interactome, showing its potential association with both histone and non-histone substrates.
Journal ArticleDOI
Uncovering cellular circuitry controlling temperature-dependent fungal morphogenesis.
Rebecca S. Shapiro,Leah E. Cowen +1 more
TL;DR: It is established that the thermally responsive molecular chaperone Hsp90 orchestrates temperature-dependent morphogenesis, via previously uncharacterized cellular circuitry, comprised of the cyclin-dependent kinase Pho85, the Cyclin Pcl1 and the transcriptional regulator Hms1.
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.
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.