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
Safrole and the Versatility of a Natural Biophore
TL;DR: The versatility of its structure, allowing various chemical transformations, and the biophoric nature of its benzodioxole or methylenedioxy subunit, make it an attractive starting material for the synthesis of compounds with different pharmacological activities.
Journal ArticleDOI
The Emerging Role of TPR-Domain Immunophilins in the Mechanism of Action of Steroid Receptors
Gisela Ileana Mazaira,Mariana Lagadari,Alejandra G. Erlejman,Mario D. Galigniana,Mario D. Galigniana +4 more
TL;DR: A group of Hsp90-binding cochaperones belonging to the immunophilin family plays a cardinal role not only in the mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity.
Journal ArticleDOI
Integration of a porous coordination network and black phosphorus nanosheets for improved photodynamic therapy of tumor.
Miao-Deng Liu,Yun Yu,Deng-Ke Guo,Shi-Bo Wang,Chu-Xin Li,Fan Gao,Cheng Zhang,Bo-Ru Xie,Zhenlin Zhong,Xian-Zheng Zhang +9 more
TL;DR: A biodegradable nanoplatform based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplplatforms in the tumor area and attenuating the protection of cancer cells is designed.
Book ChapterDOI
Detection and Analysis of Extracellular Hsp90 (eHsp90).
TL;DR: Targeting specifically the eHsp90 with pharmacologic inhibitors or antibodies that are unable to cross the plasma membrane has been beneficial in inhibiting tumor cell motility and invasion.
Journal ArticleDOI
Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32
Bhaskar K. Chatterjee,Abhilash Jayaraj,Vinay Kumar,Brian S. J. Blagg,Rachel E. Davis,Bhyravabhotla Jayaram,Shashank Deep,Tapan K. Chaudhuri +7 more
TL;DR: In vitro and in silico studies indicated that upon KU-32 binding, Hsp90 undergoes global structural changes leading to the formation of a “partially closed” intermediate that selectively binds ATP and increases ATPase activity, and it is reported that K U-32 promotes HeLa cell survival and enhances the refolding of an HSp90 substrate inside the cell.
References
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Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
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Journal ArticleDOI
HSP90 and the chaperoning of cancer.
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Journal ArticleDOI
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.
Journal ArticleDOI
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.