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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Acclimation of killifish to thermal extremes of hot spring: Transcription of gonadal and liver heat shock genes.
Arash Akbarzadeh,Erica H. Leder +1 more
TL;DR: The regulation of heat shock genes particularly hsp90a might be a key factor of the acclimation of fish to high temperature environments like hot springs.
Microenvironmental regulators of mammary gland architecture: the role of matrix metalloproteinase 3 in epithelial invasion and branching morphogenesis
TL;DR: An additional perspective is proposed, one in which the tumor cells despite the malignant genome could find a microenvironment either within the tumor or as a dormant cell to remain polar and blend into an organized context.
Journal ArticleDOI
MMPs, tyrosine kinase signaling and extracellular matrix proteolysis in kidney cancer.
TL;DR: Changes in the MMPs/ECM axis in RCC is discussed, prominent kinase signaling pathways implicated in M MPs induction are discussed, and emerging extracellular regulatory networks that modulate Mmps activity are commented on.
Journal ArticleDOI
Fungal mycotoxin penisuloxazin A, a novel C-terminal Hsp90 inhibitor and characteristics of its analogues on Hsp90 function related to binding sites.
Jiajia Dai,Meilin Zhu,Xin Qi,Yanjuan Wang,Huilin Li,Shuai Tang,Qiang Wang,Ao Chen,Ming Liu,Qianqun Gu,Dehai Li,Jing Li +11 more
TL;DR: These findings not only offer new chemotypes for anticancer drug development, but also help to better understand biological function of Hsp90 for exploring inhibitor with some client protein bias.
Journal ArticleDOI
Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils.
Pragya Prasanna,Arun Upadhyay +1 more
TL;DR: The diverse physiological importance of HSPs present in Leishmania are highlighted, emphasizing their significance in disease pathogenesis and the potential of H SPs as a chemotherapeutic target is assessed and underlined the challenges associated with it.
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.