Add time:08/29/2019 Source:sciencedirect.com
Proteostasis regulation using naturally occurring small molecules has been considered as a promising strategy for manipulating cancer sensitivity and therapy. Here, we identify a small molecule Hsp90 inhibitor RADICICOL (cas 12772-57-5) that induces intracellular accumulation of cytotoxic clusterin variant. In the mechanistic basis, this variant proved to be a product disposed from the stressed ER. During this process, inhibitory effect of radicicol on protein degradation results in cytosolic accumulation of glycan-deficient clusterin variant that signals cell death. These results provide a therapeutic insight into the targeted proteostasis perturbation of clusterin as an anti-cancer strategy.
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