Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain

Nayoung Kim, Jae Cheal Yoo, Jae Yoon Han, Eun Mi Hwang, Yoon Sook Kim, Eun Young Jeong, Choong Hyun Sun, Gwan Su Yi, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Jae Yong Park, Wan Sung Choi

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish
Pages (from-to)1157-1167
Number of pages11
JournalJournal of Cellular Physiology
Volume227
Issue number3
DOIs
Publication statusPublished - 2012 Mar
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-XL
  • Clusterin

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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