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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Marine alkaloid oroidin analogues with antiviral potential: A novel class of synthetic compounds targeting the cellular chaperone Hsp90.
TL;DR: A novel structural class of small molecules that target the Hsp90 ATP‐binding site has excellent potential for further antiviral drug development because of the compounds’ low toxicity and synthetic accessibility.
Journal ArticleDOI
TKI-addicted ROS1-rearranged cells are destined to survival or death by the intensity of ROS1 kinase activity.
Hayato Ogura,Yuka Nagatake-Kobayashi,Yuka Nagatake-Kobayashi,Jun Adachi,Takeshi Tomonaga,Naoya Fujita,Naoya Fujita,Ryohei Katayama +7 more
TL;DR: These findings partly clarify molecular mechanisms of excessive ROS1 oncogenic signaling that mediates paradoxical induction of apoptosis and recapturing the TKI-addicted phenotype.
Journal ArticleDOI
Exploring Mechanisms of Allosteric Regulation and Communication Switching in the Multiprotein Regulatory Complexes of the Hsp90 Chaperone with Cochaperones and Client Proteins : Atomistic Insights from Integrative Biophysical Modeling and Network Analysis of Conformational Landscapes.
TL;DR: In this article , a computational investigation of the Hsp90-Hsp70-Hop-CR client complex was performed to examine allosteric regulatory mechanisms underlying dynamic chaperone interactions and principles of chaperones-dependent client recognition and remodeling.
Journal ArticleDOI
Mitochondrial dysfunction and potential mitochondrial protectant treatments in tendinopathy
TL;DR: In this article, a review summarizes the potential mechanism by which mitochondrial dysfunction contributes to the development of tendinopathy, as well as the potential therapeutic benefits of mitochondrial protectants in the treatment of Tendinopathy.
Journal ArticleDOI
Identification of Pathogenic Genes and Transcription Factors in Osteosarcoma
TL;DR: The up-regulated HSP90AA1 and down-regulated BMP6 and ‘pathways in cancer’ and ’signal transduction’ were deduced to be involved in the pathogenesis of OS.
References
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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.
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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.