Cotransin induces accumulation of a cytotoxic clusterin variant that cotranslationally rerouted to the cytosol

Journal Article · Wed May 01 04:00:00 EDT 2013 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2013.01.025· OSTI ID:22278232

Choi, Ilho; Kim, Jiyeon ^[1]; Park, Joong-Yeol ^[2]; Kang, Sang-Wook ^[1]

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1. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
2. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

Although clusterin (CLU) was originally identified as a secreted glycoprotein that plays cytoprotective role, several intracellular CLU variants have been recently identified in the diverse pathological conditions. The mechanistic basis of these variants is now believed to be alternative splicing and retrotranslocation. Here, we uncovered, an unglycosylated and signal sequence-unprocessed, CLU variant in the cytosol. This variant proved to be a product that cotranslationally rerouted to the cytosol during translocation. Cytosolic CLU was prone to aggregation at peri-nuclear region of cells and induced cell death. Signal sequence is shown to be an important determinant for cytosolic CLU generation and aggregation. These results provide not only a new mechanistic insight into the cytosolic CLU generation but also an idea for therapeutic mislocalization of CLU as a strategy for cancer treatment. - Highlights: ► Intracellular CLU variants have been recently identified in the diverse pathological conditions. ► Translocation of clusterin is less efficient than that of Prl. ► We identified a new cytotoxic clusterin variant whose signal sequence was unprocessed. ► This variant proved to be a product that cotranslationally rerouted to cytosol.

• OSTI ID: 22278232
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 8 Vol. 319; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
GENES
GLYCOPROTEINS
NEOPLASMS
SIGNALS
SPLICING