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
Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1
Iaci N. Soares,Fabiana A. Caetano,Fabiana A. Caetano,Jordan Pinder,Bruna R. Rodrigues,Flavio H. Beraldo,Valeriy G. Ostapchenko,Chantal Durette,Grace S. Pereira,Marilene H. Lopes,Nicolle Queiroz-Hazarbassanov,Isabela Werneck da Cunha,Paulo Sanematsu,Sergio Hideki Suzuki,Luiz Fernando Bleggi-Torres,Caroline Schild-Poulter,Pierre Thibault,Graham Dellaire,Vilma R. Martins,Vania F. Prado,Marco A. M. Prado +20 more
TL;DR: Evidence is provided that direct interaction between STI1 and PIAS1 is involved in the accumulation of nuclear STI 1 and this retention mechanism could facilitate nuclear chaperone activity.
Journal ArticleDOI
The Co-Chaperone Hch1 Regulates Hsp90 Function Differently than Its Homologue Aha1 and Confers Sensitivity to Yeast to the Hsp90 Inhibitor NVP-AUY922
TL;DR: It is reported here that the in vivo impairment of commonly studied Hsp90 variants harbouring the G313S or A587T mutation are exacerbated by the co-chaperone Hch1p, and it is concluded that Hch 1p plays a critical role in regulating HSp90 inhibitor drug sensitivity in yeast.
Journal ArticleDOI
Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma
Phyllis R. Wachsberger,Yaacov Richard Lawrence,Yi Liu,Barbara Rice,Nicholas Feo,Benjamin E. Leiby,Adam P. Dicker +6 more
TL;DR: HSP990 and BKM120, with and without RT, are active agents against glioma tumors and the sensitivity to these agents does not appear to depend on PTEN/p53status in the cell lines tested.
Journal ArticleDOI
The Hsp90-dependent proteome is conserved and enriched for hub proteins with high levels of protein-protein connectivity.
Rajaneesh Karimpurath Gopinath,Shu-Ting You,Shu-Ting You,Kun-Yi Chien,Krishna B S Swamy,Jau-Song Yu,Scott C. Schuyler,Jun-Yi Leu +7 more
TL;DR: It is observed that downregulation of transcription factors and mating pathway components by attenuating Hsp90 function led to decreased target gene expression and pheromone response, providing a direct link between observed proteome regulation and cellular phenotypes.
Journal ArticleDOI
Chaperones and chaperone-substrate complexes: Dynamic playgrounds for NMR spectroscopists.
TL;DR: The results achieved by NMR spectroscopy are reviewed and the information content and applicability of different NMR techniques for the characterization of chaperones and chaperone-substrate complexes are assessed.
References
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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.