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
More filters
Journal ArticleDOI
Computational methods-guided design of modulators targeting protein-protein interactions (PPIs).
TL;DR: This review introduces a diverse set of computational methods used to design PPI modulators and focuses on the recent progress in computational strategies, and provides a comprehensive overview covering various methodologies.
Journal ArticleDOI
Variability in a Short Tandem Repeat Mediates Complex Epistatic Interactions in Arabidopsis thaliana.
TL;DR: The genetic architecture of the natural ELF3 polyglutamine variants cause reciprocal genetic incompatibilities in two divergent Arabidopsis thaliana backgrounds is dissected, revealing as many as four loci putatively interacting with ELF2 and supporting the proposal that highly variable STR loci can contribute to the epistatic component of heritability.
Journal ArticleDOI
A Tetrahymena Hsp90 co-chaperone promotes siRNA loading by ATP-dependent and ATP-independent mechanisms.
Sophie L Woehrer,Lucia Aronica,Jan H. Suhren,Clara Jana-Lui Busch,Tomoko Noto,Kazufumi Mochizuki +5 more
TL;DR: It is shown that Coi12p can partially restore the siRNA loading and DNA elimination defects of COI12 knockout cells, suggesting that Hsp90‐ and ATP‐independent loading of siRNA occurs in vivo and plays a physiological role in Tetrahymena.
Journal ArticleDOI
A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma
Andrea E. Wahner Hendrickson,Ann L. Oberg,Gretchen E. Glaser,John K. Camoriano,Prema P. Peethambaram,Gerardo Colon-Otero,Charles Erlichman,S. Percy Ivy,Scott H. Kaufmann,Larry M. Karnitz,Paul Haluska +10 more
TL;DR: Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.
Journal ArticleDOI
Discoidin domain receptors: a proteomic portrait.
TL;DR: An overview on the use of large-scale proteomic profiling and chemical proteomics to reveal novel insights into DDR therapeutics, signaling networks, and receptor crosstalk is provided.
References
More filters
Journal ArticleDOI
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
TL;DR: The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.