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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Journal ArticleDOI
Fine-Tuning Immunity: Players and Regulators for Plant NLRs
TL;DR: The molecular mechanisms by which NLR activities are regulated are discussed and how understanding this regulation has potential to facilitate the engineering of NLRs for crop improvement.
Journal ArticleDOI
Cumulative Impact of Chaperone-Mediated Folding on Genome Evolution
David Bogumil,Tal Dagan +1 more
TL;DR: Accumulating evidence suggests that the utility of chaperones is governed by a delicate balance between their help in mitigating the risks of protein misfolding and aggregate formation on one hand and the slower rate of protein maturation and the energetic cost of chaferone synthesis on the other.
Journal ArticleDOI
A Chaperone Trap Contributes to the Onset of Cystic Fibrosis
Judith A. Coppinger,Darren M. Hutt,Abbas Razvi,Atanas V. Koulov,Sandra Pankow,John R. Yates,William E. Balch +6 more
TL;DR: The results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation in misfolding diseases.
Journal ArticleDOI
The Hsp90 Chaperone Network Modulates Candida Virulence Traits
TL;DR: This work highlights recent work mapping the Hsp90 genetic network in C. albicans under diverse environmental conditions, and how these interactions provide insight into circuitry important for drug resistance, morphogenesis, and virulence.
Journal ArticleDOI
Molecular mechanisms of robustness in plants
TL;DR: Recent advances in identifying molecular robustness mechanisms in plants that have been enabled by a combination of classical genetics and population genetics with genome-scale data are reviewed.
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.