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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.

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Journal ArticleDOI

Hsp90 Stabilizes SIRT1 Orthologs in Mammalian Cells and C. elegans.

TL;DR: It is reported that Hsp90 is required for conformational stabilization of SIRT1 and SIR-2.1 and revealed a novel crosstalk between the proteostasis and nutrient signaling networks, which may have implications in various age related diseases.
Journal ArticleDOI

Hsp90 Maintains Proteostasis of the Galactose Utilization Pathway To Prevent Cell Lethality

TL;DR: It is observed that Hsp90 influences the protein abundance of multiple Gal proteins and the efficiency of galactose utilization even after the galactOSE utilization pathway (GAL pathway) is fully induced.
Journal ArticleDOI

Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML

TL;DR: This study has largely clarified the link between MDS and AML in terms of potential pathways, and genetic markers, which shed light on the molecular mechanisms underlying the development and transition of MDS, and facilitate the understanding of novel diagnostic, therapeutic and prognostic biomarkers.
References
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Journal ArticleDOI

Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf

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.
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