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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RPL1, a gene involved in epigenetic processes regulates phenotypic plasticity in rice.
TL;DR: Analysis of the putative rice brassinosteroid receptor OsBRI1, a key hormone signaling gene, indicated that RPL1 may be involved in the regulation of epigenomic modification of the gene, suggesting regulated phenotypic plasticity likely through its involvement in epigenetic processes affecting responses of the plant to phytohormones.
Journal ArticleDOI
Interplay between chaperones and protein disorder promotes the evolution of protein networks.
TL;DR: Both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance, which highlights an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks.
Journal ArticleDOI
Molecular chaperone Hsp90 as a target for oxidant-based anticancer therapies.
Raphaël Beck,Nicolas Dejeans,Christophe Glorieux,Rozangela Curi Pedrosa,David Vásquez,Jaime A. Valderrama,Pedro Buc Calderon,Julien Verrax +7 more
TL;DR: The results show that oxidative stress provokes the cleavage of Hsp90 in CML cells, as well as the degradation of its client protein Bcr-Abl and the deactivation of its downstream signaling pathways, namely MAPK and STAT5.
Journal ArticleDOI
A switch point in the molecular chaperone Hsp90 responding to client interaction.
Daniel A. Rutz,Qi Luo,Qi Luo,Lee Freiburger,Tobias Madl,Ville R. I. Kaila,Michael Sattler,Johannes Buchner +7 more
TL;DR: The study shows that this conserved tryptophan senses the interaction of Hsp90 with a stringent client protein and transfers this information via a cation–π interaction with a neighboring lysine, which allows HSp90 to transmit information on the binding of a client from H Sp90-M to Hsp 90-N which is important for progression of the conformational cycle and the efficient processing of client proteins.
Journal ArticleDOI
Cosuppression of the chloroplast localized molecular chaperone HSP90.5 impairs plant development and chloroplast biogenesis in Arabidopsis.
TL;DR: Transgenic Arabidopsis plants that overexpress a C-terminally FLAG-tagged HSP90.5 cosuppression line are generated, and it is demonstrated that properly controlled expression of HSP 90.5 is required for plant growth and development in many tissues, and especially essential for chloroplast thylakoid formation.
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.