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

  • J Cell Physiol. 2012 Mar;227(3):1157-67. doi: 10.1002/jcp.22836.
Nayoung Kim  1 ,  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
Affiliations
  • 1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam, South Korea.
PMID: 21567405 DOI: 10.1002/jcp.22836
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.