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
The yeast Hsp70 Ssa1 is a sensor for activation of the heat shock response by thiol-reactive compounds.
TL;DR: Diverse thiol-reactive compounds are found to activate the Hsf1-regulated heat shock response in Saccharomyces cerevisiae and the highly conserved cytosolic Hsp70 protein chaperone is shown to act as a sensor for these molecules through a pair of reactive cysteine residues in the nucleotide-binding domain.
Journal ArticleDOI
Hsp90 inhibition protects against inherited retinal degeneration
Mònica Aguilà,Dalila Bevilacqua,Caroline McCulley,Nele Schwarz,Dimitra Athanasiou,Naheed Kanuga,Sergey S. Novoselov,Clemens Lange,Robin R. Ali,James W B Bainbridge,Carlos Gias,Peter J. Coffey,Pere Garriga,Michael E. Cheetham +13 more
TL;DR: It is shown that a single low dose of the Hsp90 inhibitor HSP990 enhanced visual function and delayed photoreceptor degeneration in a P23H transgenic rat model, but also indicates that sustained HSp90 inhibition might adversely affect visual function.
Journal ArticleDOI
Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells
Chia-Lung Tsai,Chi-Neu Tsai,Chiao-Yun Lin,Hsi-Wen Chen,Yun-Shien Lee,Yun-Shien Lee,Angel Chao,Tzu-Hao Wang,Tzu-Hao Wang,Hsin-Shih Wang,Chyong-Huey Lai +10 more
TL;DR: Ov ovarian-cancer-tissue-secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways, which may pave the way for developing novel therapeutic strategies for ovarian cancer.
Journal ArticleDOI
Jujuboside A promotes Aβ clearance and ameliorates cognitive deficiency in Alzheimer's disease through activating Axl/HSP90/PPARγ pathway.
Mu Zhang,Cheng Qian,Zu-Guo Zheng,Fei Qian,Yanyan Wang,Pyone Myat Thu,Xin Zhang,Ya-Ping Zhou,Li-Fan Tu,Qingling Liu,Hui-Jun Li,Hua Yang,Ping Li,Xiaojun Xu +13 more
TL;DR: This study suggests that the up-regulation of HSP90β by JuA through Axl is a potential therapeutic strategy to facilitate Aβ42 clearance and ameliorate cognitive deficiency in AD.
Journal ArticleDOI
Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands
Gerolamo Vettoretti,Elisabetta Moroni,Sara Sattin,Jiahui Tao,David A. Agard,Anna Bernardi,Giorgio Colombo +6 more
TL;DR: This study examines the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics simulations and analysis of protein-ligand interactions, and discusses the implications of considering the conformational dialogue betweenallosteric ligands and protein conformations for the design of new functional modulators.
References
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