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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Genome sequence of Saccharomyces carlsbergensis, the world's first
TL;DR: Evidence for genome and chromosome evolution within S. carlsbergensis via chromosome loss and loss of heterozygosity specifically of parts derived from the S. cerevisiae parent is presented and a joint evolutionary ancestry for lager yeast strains is proposed.
Journal ArticleDOI
Explaining bathymetric diversity patterns in marine benthic invertebrates and demersal fishes: physiological contributions to adaptation of life at depth
Alastair Brown,Sven Thatje +1 more
TL;DR: The hypothesise that demonstrated physiological effects of high hydrostatic pressure and low temperature at bathyal depths, acting on shallow‐water taxa invading the deep sea, may invoke a stress–evolution mechanism by increasing mutagenic activity in germ cells, by inactivating canalisation during embryonic or larval development, by releasing hidden variation or mutagenics activity, or by activating or releasing transposable elements in larvae or adults.
Journal ArticleDOI
Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthritis-associated interstitial lung disease.
Lisa Harlow,Ivan O. Rosas,Bernadette R. Gochuico,Ted R. Mikuls,Paul F. Dellaripa,Chester V. Oddis,Dana P. Ascherman +6 more
TL;DR: These studies demonstrate the utility of a novel autoantigen discovery method based on differential immunoprecipitation of citrullinated protein extracts for the potentially devastating pulmonary manifestations of RA-ILD.
Journal ArticleDOI
GIGANTEA is a co-chaperone which facilitates maturation of ZEITLUPE in the Arabidopsis circadian clock
Joon-Yung Cha,Jeongsik Kim,Tae-Sung Kim,Tae-Sung Kim,Qingning Zeng,Lei Wang,Lei Wang,Sang Yeol Lee,Woe-Yeon Kim,David E. Somers +9 more
TL;DR: It is shown that GIGANTEA has intrinsic chaperone activity and can facilitate ZEITLUPE maturation by acting synergistically with HSP90, and a molecular mechanism for GIGantEA activity is identified that can explain its wide-ranging role in plant biology.
Journal ArticleDOI
The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.
Jae Ho Seo,Dayana B. Rivadeneira,M. Cecilia Caino,Young Chan Chae,David W. Speicher,Hsin Yao Tang,Valentina Vaira,Valentina Vaira,Silvano Bosari,Silvano Bosari,Alessandro Palleschi,Paolo Rampini,Andrew V. Kossenkov,Lucia R. Languino,Lucia R. Languino,Dario C. Altieri +15 more
TL;DR: Tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence, and this pathway may provide a “drugable” therapeutic target in cancer.
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.