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
Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle
TL;DR: At distinct steps during the HSp90 chaperone cycle, co-chaperones selectively trap statistically distributed Hsp90 conformers and thus turn Hsp 90 into a deterministic machine.
Journal ArticleDOI
ALK inhibitors in non-small cell lung cancer: the latest evidence and developments.
Ivana Sullivan,David Planchard +1 more
TL;DR: This review focuses on the molecular and clinical properties of this new generation of ALK inhibitors under development in the clinic for crizotinib-resistant NSCLC.
Journal ArticleDOI
Development of a Mitochondria-Targeted Hsp90 Inhibitor Based on the Crystal Structures of Human TRAP1
Changwook Lee,Hye-Kyung Park,Hanbin Jeong,Jaehwa Lim,An-Jung Lee,Keun Young Cheon,Chul-Su Kim,Ajesh P. Thomas,Boram Bae,Nam Doo Kim,Seong Heon Kim,Pann-Ghill Suh,Ja-Hyoung Ryu,Byoung Heon Kang +13 more
TL;DR: It is reported that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP 1 because of their insufficient accumulation in the mitochondria.
Journal ArticleDOI
Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s
Young Chan Chae,M. Cecilia Caino,Sofia Lisanti,Jagadish C. Ghosh,Takehiko Dohi,Nika N. Danial,Jessie Villanueva,Stefano Ferrero,Valentina Vaira,Valentina Vaira,Luigi Santambrogio,Silvano Bosari,Lucia R. Languino,Lucia R. Languino,Meenhard Herlyn,Dario C. Altieri +15 more
TL;DR: It is shown that heat-shock-protein-90-directed protein folding in mitochondria, but not cytosol, maintains energy production in tumor cells, and mitochondrial heat shock protein 90s are adaptive regulators of tumor bioenergetics and tractable targets for cancer therapy.
Journal ArticleDOI
Dermatophyte Resistance to Antifungal Drugs: Mechanisms and Prospectus.
Nilce Maria Martinez-Rossi,Tamires Aparecida Bitencourt,Nalu T. A. Peres,Elza A. S. Lang,Eriston Vieira Gomes,Natália Renault Quaresemin,Maíra Pompeu Martins,Lucia Rossetti Lopes,Antonio Rossi +8 more
TL;DR: An understanding of the molecular mechanisms involved in the resistance/tolerance processes, the identification of new antifungal targets, as well as the prospective of new anti-fungal compounds among natural or synthetic products, are expected to bring advances and new insights that facilitate the improvement or development of novel strategies for antIfungal therapy.
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.
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.
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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.