Original Research Article
Human Nuclear Clusterin Mediates Apoptosis by Interacting with Bcl-XL
through C-terminal Coiled Coil Domain
Nayoung Kim1 Jae Cheal Yoo2, Jae Yoon Han1, Eun Mi Hwang2, Yoon Sook Kim1, Eun
Young Jeong1, Choong-Hyun Sun3, Gwan-Su Yi3, Gu Seob Roh1, Hyun Joon Kim1, Sang
Soo Kang1, Gyeong Jae Cho1, Jae Yong Park2,*, Wan Sung Choi1,*
1Department of Anatomy and Neurobiology, Medical Research Center for Neural
Dysfunction, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju,
Gyeongnam 660-751, South Korea; 2Department of Physiology, School of Medicine,
Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam 660-751, South Korea;
3Department of Bio and Brain Engineering, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon
305-701, South Korea
Corresponding authors
*Address correspondence to: W.S. Choi, Prof. Department of Anatomy and Neurobiology,
Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National
University, 92 Chilam-dong, Jinju, Gyeongnam 660-751, South Korea. Tel: +82-55-751-8731,
Fax: +82-55-759-0779, E-mail: choiws@gnu.ac.kr; and J.Y. Park, Prof. Department of
Physiology, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju,
Gyeongnam 660-751, South Korea. Tel: +82-55-751-8743, Fax: +82-55-759-0169, E-mail:
jaeyong@gnu.ac.kr.
Running head: Nuclear clusterin interacts with Bcl-XL
Keywords: Clusterin, apoptosis, Bcl-XL
Contract grant sponsor: the MRC program of National Research Foundation of Korea;
Contract grant number: R13-2005-012-01001-1
Abbreviations
a.a., Amino acid
Ab, antibody
BH3, Bcl-2 homology 3
CC, coiled coil
CC2, C-terminal coiled coil
CLU, clusterin
nCLU, nuclear CLU
pnCLU, precursor nCLU
psCLU, precursor sCLU
sCLU, secretory CLU
WT, wild type
Additional Supporting Information may be found in the online version of this article.
Received 29 December 2010; Revised 11 April 2011; Accepted 4 May 2011
Journal of Cellular Physiology
© 2011 Wiley-Liss, Inc.
DOI 10.1002/jcp.22836
1

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.
2