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
Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension.
Guokun Wang,Song-Hua Li,Zhi-Min Zhao,Suxuan Liu,Guan-xin Zhang,Fan Yang,Yang Wang,Feng Wu,Xianxian Zhao,Zhiyun Xu +9 more
TL;DR: HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH.
Journal ArticleDOI
Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1).
Flavio H. Beraldo,Anu Alice Thomas,Benjamin Kolisnyk,Pedro H. Hirata,Xavier De Jaeger,Amanda C. Martyn,Jue Fan,Daniela F. Goncalves,Matthew F. Cowan,Talal S. Masood,Vilma R. Martins,Robert Gros,Vania F. Prado,Marco A. M. Prado +13 more
TL;DR: It is concluded that reduced STIP1 levels can contribute to phenotypes related to ASD, however, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes.
Journal ArticleDOI
Targeting the Hsp90 C-terminal domain by the chemically accessible dihydropyrimidinone scaffold
Maria Strocchia,Stefania Terracciano,Maria Giovanna Chini,Antonio Vassallo,Maria C. Vaccaro,Fabrizio Dal Piaz,Antonietta Leone,Raffaele Riccio,Ines Bruno,Giuseppe Bifulco +9 more
TL;DR: The identification of a new dihydropyrimidinone binding the C-terminus is reported, which is not structurally related to other well-known natural and nature-inspired inhibitors of this second druggable Hsp90 site.
Journal ArticleDOI
Heterozygous yeast deletion collection screens reveal essential targets of Hsp90.
TL;DR: The integrated analysis of the 15°C heterozygous deletion pool screen with previously conducted 30°C and 37°C screens allows for essential genetic targets of Hsp90 to emerge and enables a more complete picture of essential Hsp 90 functions.
Journal ArticleDOI
Folding and Domain Interactions of Three Orthologs of Hsp90 Studied by Single-Molecule Force Spectroscopy
Markus Jahn,Katarzyna M. Tych,Hannah Girstmair,Maximilian Steinmaßl,Thorsten Hugel,Johannes Buchner,Matthias Rief +6 more
TL;DR: The domain interactions mediated by the charged linker, involved in the conformational cycles of all three orthologs, are much stronger for Grp94 than for Hsp82, keeping the N-terminal domain and the middle domain in close proximity.
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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Function and regulation of cullin-RING ubiquitin ligases.
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