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
Heat Shock Protein 90 regulates encystation in Entamoeba.
TL;DR: It is shown that Hsp90 plays an important role in virulence and transmission of Entamoeba, and is identified to be a negative regulator of encystation in EntamoEBa.
Journal ArticleDOI
A methylated lysine is a switch point for conformational communication in the chaperone Hsp90
Alexandra Rehn,Jannis Lawatscheck,Marie-Lena Jokisch,Sophie L. Mader,Qi Luo,Qi Luo,Franziska Tippel,Birgit Blank,Birgit Blank,Klaus Richter,Kathrin Lang,Ville R. I. Kaila,Ville R. I. Kaila,Johannes Buchner +13 more
TL;DR: It is demonstrated that this particular lysine serves as a switch point for the regulation of Hsp90 functions by influencing its conformational cycle, ATPase activity, co-chaperone regulation, and client activation of yeast and human HSp90.
Journal ArticleDOI
Scrib regulates HGF-mediated epithelial morphogenesis and is stabilized by Sgt1-HSP90.
TL;DR: The identification of Scrib as an Sgt1–HSP90 client protein required for three-dimensional cell migration suggests that chaperone-mediated regulation of polarity protein stability and homeostasis is an unappreciated mechanism underlying dynamic rearrangements during morphogenesis.
Journal ArticleDOI
Estimation of Protein–Ligand Unbinding Kinetics Using Non-Equilibrium Targeted Molecular Dynamics Simulations
Steffen Wolf,Steffen Wolf,Marta Amaral,Maryse Lowinski,François Vallée,Djordje Musil,Jörn Güldenhaupt,Matthias K. Dreyer,Jörg Bomke,Matthias Frech,Jürgen Schlitter,Klaus Gerwert +11 more
TL;DR: In this paper, nonequilibrium targeted molecular dynamics simulations were used for the estimation of protein-ligand unbinding kinetics, and the results were correlated with experimental data from SPR k-means.
Journal ArticleDOI
Development of a novel Hsp90 inhibitor NCT-50 as a potential anticancer agent for the treatment of non-small cell lung cancer
Seung Yeob Hyun,Huong Thuy Le,Cong Truong Nguyen,Young Sik Yong,Hye Jin Boo,Ho Jin Lee,Ji Sun Lee,Hye-Young Min,Jihyae Ann,Jie Chen,Hyun Ju Park,Jeewoo Lee,Ho-Young Lee +12 more
TL;DR: NCT-50 as mentioned in this paper is a novobiocin-deguelin analog hybridizing the pharmacophores of these known Hsp90 inhibitors and showed significant inhibitory effects on the viability and colony formation of non-small cell lung cancer (NSCLC) cells and those carrying resistance to chemotherapy.
References
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