2. Academic Validation
  3. Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain

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

Affiliation

  • 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.

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