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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Mutually Synergistic Nanoparticles for Effective Thermo-Molecularly Targeted Therapy
Huanhuan Luo,Qiaoli Wang,Yibin Deng,Tao Yang,Hengte Ke,Hong Yang,Hui He,Zhengqing Guo,Dong Yu,Hong Wu,Huabing Chen +10 more
TL;DR: A rational fabrication of the micelles that can achieve mutual synergy of PTT and molecularly targeted therapy (MTT) for tumor ablation is reported, and these findings represent a general approach for potent cancer therapy.
Journal ArticleDOI
HSP90 as a platform for the assembly of more effective cancer chemotherapy.
Luke Whitesell,Nan Lin +1 more
TL;DR: This review will focus on how the utilization of HSP90 by cancer cells might be targeted to enhance the activity of other anticancer drugs while at the same time limiting the ability of advanced cancers to adapt and evolve drug resistance; the net result being more durable disease control.
Journal ArticleDOI
Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs
TL;DR: It is proposed that Hsp90 acts as a biological transistor that modulates the activity of fungal signalling networks in response to environmental cues via this Hsf1–Hsp90 autoregulatory loop.
Journal ArticleDOI
Targeting heat shock proteins in metastatic castration-resistant prostate cancer
TL;DR: The integral role of HSPs in AR function speaks to their potential utility as therapeutic targets in castration-resistant prostate cancer (CRPC), a disease state characterized by persistent activation of the androgen–AR axis.
Journal ArticleDOI
Adaptive Mitochondrial Reprogramming and Resistance to PI3K Therapy
Jagadish C. Ghosh,Markus D. Siegelin,Valentina Vaira,Alice Faversani,Michele Tavecchio,Young Chan Chae,Sofia Lisanti,Paolo Rampini,Massimo Giroda,M. Cecilia Caino,Jae Ho Seo,Andrew V. Kossenkov,Ryan D. Michalek,David C. Schultz,Silvano Bosari,Lucia R. Languino,Dario C. Altieri +16 more
TL;DR: Novel combination therapies that target mitochondrial adaptation can dramatically improve on the efficacy of PI3K therapy in the clinic, and promote drug resistance by repurposing mitochondrial functions in bioenergetics and cell survival.
References
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Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
Paul T C Wan,Mathew J. Garnett,S. Mark Roe,Sharlene Lee,Dan Niculescu-Duvaz,Valerie M. Good,Cancer Genome,C. Michael Jones,Christopher J. Marshall,Caroline J. Springer,David Barford,Richard Marais +11 more
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HSP90 and the chaperoning of cancer.
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.