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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FGFR3 biology and skeletal disease.
Jyoti Narayana,William A. Horton +1 more
TL;DR: Fibroblast Growth Factor Receptor 3 is one of four high-affinity receptors for canonical FGF ligands that acts in many tissues and plays a special role in skeletal development, especially post-embryonic bone growth, where it inhibits chondrocyte proliferation and differentiation.
Journal ArticleDOI
Hsp90β interacts with MDM2 to suppress p53‐dependent senescence during skeletal muscle regeneration
Min Yi He,Shui Bo Xu,Zi Hao Qu,Yue Mei Guo,Xiao Ceng Liu,Xiao Xia Cong,Jian Feng Wang,Boon Chuan Low,Li Li,Qiang Wu,Peng Lin,Shi Gui Yan,Zhang Bao,Yi Ting Zhou,Li Ling Zheng +14 more
TL;DR: A previously unappreciated role of Hsp90β is revealed in regulating p53 stability to suppress senescence both in vitro and in vivo.
Journal ArticleDOI
Physiological consequences of mutations in the htpG heat shock gene of Escherichia coli
TL;DR: Assays based on bioluminescence and crystal violet staining demonstrated that biofilm formation was diminished in the ΔhtpG mutant at the elevated temperature, and these defects can be complemented upon introducing htpG wild allele.
Journal ArticleDOI
Epigenetic Alterations of Heat Shock Proteins (HSPs) in Cancer.
TL;DR: The epigenetic alterations of HSP expression in cancer cells are described and it is suggested that HSPs be clinically applied as diagnostic and therapeutic markers in cancer therapy via controlled epigenetic modifiers.
Journal ArticleDOI
Hsp90 Inhibitors for the Treatment of Chronic Myeloid Leukemia.
TL;DR: The present review targets the current development in the CML treatment by availing Hsp90 specific inhibitors, which successfully block CML progression by destabilizing the binding of BCR-ABL protein thus leading to the formation of heteroprotein complex that is eventually degraded by the ubiquitin-proteasome pathway.
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.