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
Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease
John P. Labbadia,Helen E. Cunliffe,Andreas Weiss,Elena Katsyuba,Kirupa Sathasivam,Tamara Seredenina,Ben Woodman,Saliha Moussaoui,Stefan Frentzel,Ruth Luthi-Carter,Paolo Paganetti,Gillian P. Bates +11 more
TL;DR: The findings reveal that the HSR, a major inducible regulator of protein homeostasis and longevity, is disrupted in HD, and pharmacological induction of HSF1 as a therapeutic approach to HD is more complex than was previously anticipated.
Journal ArticleDOI
A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis.
Qiyu Feng,Chengliang Zhang,David H. Lum,Joseph E. Druso,B. Blank,Kristin F. Wilson,Alana L. Welm,Marc A. Antonyak,Richard A. Cerione +8 more
TL;DR: A novel mechanism by which cancer cell-derived MVs influence the tumour microenvironment is revealed and the importance of recognizing their unique properties when considering drug treatment strategies is highlighted.
Journal ArticleDOI
Emerging picture of host chaperone and cyclophilin roles in RNA virus replication.
TL;DR: The emerging roles of cyclophilins, which are peptidyl-prolyl isomerases with chaperone functions, in replication of selected (+)RNA viruses are discussed.
Journal ArticleDOI
Striatal neurons directly converted from Huntington's disease patient fibroblasts recapitulate age-associated disease phenotypes.
Matheus B. Victor,Michelle Richner,Hannah E. Olsen,Seong Won Lee,Alex Mas Monteys,Chunyu Ma,Christine J. Huh,Bo Zhang,Beverly L. Davidson,Beverly L. Davidson,X. William Yang,Andrew S. Yoo +11 more
TL;DR: Direct neuronal conversion of skin fibroblasts from individuals with Huntington’s disease generates a population of medium spiny neurons that recapitulate hallmarks of HD, including aggregation of mutant huntingtin protein, DNA damage and spontaneous cell death.
Journal ArticleDOI
Prospects of engineering thermotolerance in crops through modulation of heat stress transcription factor and heat shock protein networks.
TL;DR: There is increasing evidence that the originally assumed specialized function of Hsf/chaperone networks in the HSR turns out to be a complex central stress response system that is involved in the regulation of a broad variety of other stress responses and may also have substantial impact on various developmental processes.
References
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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.
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