Regular ArticleThe Benzoquinone Ansamycin Geldanamycin Stimulates Proteolytic Degradation of Focal Adhesion Kinase
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Targeting heat shock protein 90 for anti-cancer drug development
2021, Advances in Cancer ResearchCitation Excerpt :For example, focal-adhesion kinase (FAK) and integrin linked kinase (ILK) are two key players promoting cell-adhesion. Inhibition of HSP90 stimulates the protease-mediated degradation of FAK and ILK in a variety of cancer cells (Aoyagi, Fujita, & Tsuruo, 2005; Ochel, Schulte, Nguyen, Trepel, & Neckers, 1999). Hepatocyte growth factor (HGF) stimulates cell motility and angiogenesis via the activation of a downstream tyrosine kinase signaling cascade.
Targeted cancer therapy through 17-DMAG as an Hsp90 inhibitor: Overview and current state of the art
2018, Biomedicine and PharmacotherapyHeat Shock Proteins and Cancer
2017, Trends in Pharmacological SciencesExpression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG
2014, Pathology Research and PracticeCitation Excerpt :It is important to appreciate that the stability and functional conformation of FAK is dependent on the chaperone functions of the heat shock protein 90 (Hsp90). In fact, inhibition of Hsp90 stimulates the proteasome-mediated degradation of FAK [5] and interferes with its phosphorylation [6]. FAK's sensitivity to the destabilizing effects of Hsp90 inhibitors is a feature worth characterizing in UM, as it holds practical value in attenuating FAK activity.
N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin-N-acetylcysteine adduct
2014, Chemico-Biological InteractionsCitation Excerpt :GDN specifically binds and inhibits heat shock protein 90 (Hsp90), a molecular chaperone whose association is required for the proper folding, stability, and function of multiple mutated and over-expressed signaling proteins that promote the growth and survival of cancer cells. Inhibition of Hsp90 causes a destabilization and eventual degradation of its client proteins such as protein kinases, including cyclin dependent kinase 4 (cdk4), Bcr-Abl tyrosine kinase, protein kinase B (PKB/Akt), and focal adhesion kinase (FAK); growth factor receptors, including epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR); hypoxia-inducible factor 1α (HIF-1α); mutated p53; and telomerase [4–9]. Inhibition of Hsp90 by GDN induces degradation of multiple oncogenic proteins which leads to a blockade of signaling pathways that maintain proliferation and survival of cancer cells and eventually results in cell death [10,11].
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