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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Hsp90 Is Essential under Heat Stress in the Bacterium Shewanella oneidensis
TL;DR: The Hsp90 chaperone is essential in eukaryotes and activates a large array of client proteins, and its role is still elusive in bacteria, and only a few Hsp80 bacterial clients are known; this study links the essentiality of bacterial Hsp 90 at high temperature with the identification of a client.
Journal ArticleDOI
DEPTOR is a direct NOTCH1 target that promotes cell proliferation and survival in T-cell leukemia
Yibing Hu,H Su,Chang Liu,Zhihui Wang,Liang Huang,Q Wang,S Liu,S Chen,J Zhou,Peng Li,Zhaohui Chen,Hudan Liu,Guoliang Qing +12 more
TL;DR: A novel mechanism involved in NOTCH1-driven leukemogenesis is revealed, identifying the transcriptional control of DEPTOR and its regulation of AKT as additional key elements of the leukeMogenic program activated by NotCH1.
Journal ArticleDOI
Characterization of the Proteostasis Roles of Glycerol Accumulation, Protein Degradation and Protein Synthesis during Osmotic Stress in C. elegans
TL;DR: It is demonstrated directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function.
Journal ArticleDOI
Allosteric Regulation of the Hsp90 Dynamics and Stability by Client Recruiter Cochaperones: Protein Structure Network Modeling
TL;DR: It is found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins.
Journal ArticleDOI
The endoplasmic reticulum: A hub of protein quality control in health and disease
TL;DR: The components of the ERQC machinery are described, their response to different forms of stress are investigated, and the consequences of ERZC break‐down are discussed.
References
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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.