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
Molecular basis of the interaction of Hsp90 with its co-chaperone Hop.
TL;DR: A combinatory approach comprising native polyacrylamide gel electrophoresis, multiangle light scattering, isothermal titration calorimetry, small‐angle X‐ray scattering, dynamic light scattering and nuclear magnetic resonance, spectroscopy is employed to obtain a comprehensive picture about the human Hsp90β:Hop association in solution.
Journal ArticleDOI
Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells.
Daniela Kramer,Nadine Stark,Ramona Schulz-Heddergott,Norman Erytch,Shelley Edmunds,Laura Roßmann,Holger Bastians,Nicole Concin,Ute M. Moll,Ute M. Moll,Matthias Dobbelstein +10 more
TL;DR: The findings indicate that ganetespib strongly potentiates the antitumor efficacy of carboplatin by causing combined inhibition of DNA repair and cell cycle control mechanisms, thus triggering global chromosome disruption, aberrant mitosis and cell death.
Book ChapterDOI
A Multicolor Single-Molecule FRET Approach to Study Protein Dynamics and Interactions Simultaneously.
TL;DR: The power and limitations of multicolor smFRET experiments are demonstrated including the description of a multi-color smFret setup and data analysis and a general analytical procedure is presented and applied to the multicomponent heat shock protein 90 system.
Journal ArticleDOI
BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation.
Xintong Wang,Cihang Bao,Yibin Jia,Nana Wang,Wei Ma,Fang Liu,Cong Wang,Jianbo Wang,Qingxu Song,Yufeng Cheng +9 more
TL;DR: The results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.
Journal ArticleDOI
Mountain ginseng inhibits skeletal muscle atrophy by decreasing muscle RING finger protein-1 and atrogin1 through forkhead box O3 in L6 myotubes.
TL;DR: It is suggested that mountain ginseng inhibits skeletal muscle atrophy by decreasing MuRF1 and atrogin1 through FOXO3a in L6 myotubes in DEXA-induced rats.
References
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Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
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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.