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Biochem Biophys Res Commun. 2015 Mar 13;458(3):555-560. doi: 10.1016/j.bbrc.2015.02.005. Epub 2015 Feb 11.

Radicicol induces intracellular accumulation of glycan-deficient clusterin variant.

Author information

1
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
2
Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
3
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea. Electronic address: swkang@amc.seoul.kr.

Abstract

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 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.

KEYWORDS:

Clusterin; ER stress; Proteostasis; Radicicol

PMID:
25680466
DOI:
10.1016/j.bbrc.2015.02.005
[Indexed for MEDLINE]

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