Abstract
Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule.
Original language | English |
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Pages (from-to) | 1157-1167 |
Number of pages | 11 |
Journal | Journal of Cellular Physiology |
Volume | 227 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2012 Mar |
Externally published | Yes |
Keywords
- Apoptosis
- Bcl-XL
- Clusterin
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology