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
Posttranslational modification and conformational state of heat shock protein 90 differentially affect binding of chemically diverse small molecule inhibitors.
Kristin Beebe,Mehdi Mollapour,Bradley T. Scroggins,Chrisostomos Prodromou,Wanping Xu,Mari Tokita,Tony Taldone,Lester Pullen,Bettina K. Zierer,Min-Jung Lee,Jane B. Trepel,Johannes Buchner,Daniel N. Bolon,Gabriela Chiosis,Leonard M. Neckers +14 more
TL;DR: It is demonstrated that two chemically unrelated Hsp90 inhibitors, the benzoquinone ansamycin geldanamycin and the purine analog PU-H71, select for overlapping but not identical subpopulations of total cellular HSp90, even though both inhibitors bind to an amino terminal nucleotide pocket and prevent N domain dimerization.
Journal ArticleDOI
Heat shock protein 90 in Alzheimer's disease.
TL;DR: Recent advances and challenges in targeting Hsp90 for AD therapy are discussed, which may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70.
Journal ArticleDOI
Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity.
Annerleim Walton-Diaz,Sahar Khan,Dimitra Bourboulia,Jane B. Trepel,Len Neckers,Mehdi Mollapour +5 more
TL;DR: The impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.
Journal ArticleDOI
Drought stress-induced physiological mechanisms, signaling pathways and molecular response of chloroplasts in common vegetable crops.
Kaukab Razi,Sowbiya Muneer +1 more
TL;DR: In this article, the chloroplast, organelle responsible for photosynthesis, is found to counteract the ill effects of drought stress by its critical involvement as a sensor of changes occurring in the environment, as the first process that drought stress affects is photosynthesis.
Journal ArticleDOI
Does the central dogma still stand
TL;DR: There is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology.
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.
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.