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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Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins
Jennifer R. Smith,E de Billy,S M Hobbs,Marissa V. Powers,Chrisostomos Prodromou,Chrisostomos Prodromou,Laurence H. Pearl,Laurence H. Pearl,Paul A. Clarke,Paul Workman +9 more
TL;DR: It is demonstrated that CDC37 can stabilise kinase clients by a mechanism that is not dependent on a substantial direct interaction between CDC37 and HSP90, but nevertheless requires HSP 90 activity.
Journal ArticleDOI
Sequencing-based gene network analysis provides a core set of gene resource for understanding thermal adaptation in Zhikong scallop Chlamys farreri.
Xiaoteng Fu,Yan Sun,Jingfeng Wang,Qiang Xing,Jiajun Zou,Ruojiao Li,Zhigang Wang,Shi Wang,Xiaoli Hu,Lingling Zhang,Zhenmin Bao +10 more
TL;DR: This study represents the first sequencing‐based gene network analysis in a nonmodel aquatic species and provides valuable gene resources for the study of thermal adaptation, which should assist in the development of heat‐tolerant scallop lines for aquaculture.
Journal ArticleDOI
Heat acclimation attenuates physiological strain and the Hsp72, but not Hsp90α mRNA response to acute normobaric hypoxia
TL;DR: HSP72 and HSP90α mRNA increased in response to each HA session, but did not change with CON, and O2 saturation higher at 65% V̇O2 peak following HA, but not CON, which induced greater rectal temperatures, sweat rate, and heart rates than CON during the training sessions.
Journal ArticleDOI
Design and Synthesis of Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors.
David S. Huang,Emmanuelle V. LeBlanc,Tanvi Shekhar-Guturja,Nicole Robbins,Damian J. Krysan,Juan C. Pizarro,Luke Whitesell,Leah E. Cowen,Lauren E. Brown +8 more
TL;DR: A series of synthetic aminopyrazole-substituted resorcylates with broad, potent, and fungal-selective Hsp90 inhibitory activity is developed, as well as the structure-activity relationships driving selectivity for Cryptococcus neoformans and Candida albicans, two pathogenic fungi of major clinical importance.
Journal ArticleDOI
TYK2: An Upstream Kinase of STATs in Cancer
TL;DR: This review focuses on the recent findings describing the oncogenic potential of the protein tyrosine kinase 2 (TYK2) and the activation of the signal transducers and activators of transcription (STAT) 3 and 5.
References
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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.