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
mTOR inhibition potentiates HSP90 inhibitor activity via cessation of HSP synthesis.
Jaime Acquaviva,Suqin He,Jim Sang,Donald L. Smith,Manuel Sequeira,Chaohua Zhang,Richard C. Bates,David A. Proia +7 more
TL;DR: Combined therapy regimens with mTOR or dual PI3K/mTOR inhibitors potentiated the antitumor efficacy of ganetespib in multiple in vivo models, indicating that mTOR blockade confers a negative regulatory effect on HSF1 activity.
Journal ArticleDOI
A systematic atlas of chaperome deregulation topologies across the human cancer landscape.
Ali Hadizadeh Esfahani,Angelina Sverchkova,Julio Saez-Rodriguez,Julio Saez-Rodriguez,Andreas Schuppert,Marc Brehme +5 more
TL;DR: This study showcases a comprehensive profiling of chaperome shifts in human cancers and sets the stage for a systematic global analysis of PN alterations across the human diseasome towards novel hypotheses for therapeutic network re-adjustment in proteostasis disorders.
Journal ArticleDOI
Multiple capacitors for natural genetic variation in Drosophila melanogaster.
TL;DR: It is suggested that CGV in wing shape of wild‐type D. melanogaster is regulated by multiple capacitors with divergent functions, and 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome.
Journal ArticleDOI
Inhibition of Heat Shock Protein 90 Prevents HIV Rebound
TL;DR: In vivo evidence is provided that inhibition of Hsp90 activity prevents HIV gene expression in replication-competent cellular reservoirs that would typically cause rebound in plasma viremia after antiretroviral therapy cessation, and this work was able to recover infectious HIV from PBMC with heat shock.
Journal ArticleDOI
An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols
Ka Chung Tong,Chun-Nam Lok,Pui Ki Wan,Di Hu,Yi Man Eva Fung,Xiao Yong Chang,Song Huang,Haibocc Jiang,Chi-Ming Che +8 more
TL;DR: A distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer activities is unequivocally demonstrated.
References
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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.