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

Authors

  • Nayoung Kim,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Jae Cheal Yoo,

    1. Department of Physiology, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Jae Yoon Han,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Eun Mi Hwang,

    1. Department of Physiology, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Current affiliation:
    1. Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, South Korea.
    Search for more papers by this author
  • Yoon Sook Kim,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Eun Young Jeong,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Choong-Hyun Sun,

    1. Department of Bio and Brain Engineering, KAIST, Daejeon, South Korea
    Search for more papers by this author
  • Gwan-Su Yi,

    1. Department of Bio and Brain Engineering, KAIST, Daejeon, South Korea
    Search for more papers by this author
  • Gu Seob Roh,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Hyun Joon Kim,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Sang Soo Kang,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Gyeong Jae Cho,

    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    Search for more papers by this author
  • Jae-Yong Park,

    Corresponding author
    1. Department of Physiology, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    • Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, South Korea.
    Search for more papers by this author
  • Wan Sung Choi

    Corresponding author
    1. Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Gyeongnam, South Korea
    • 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.
    Search for more papers by this author

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. J. Cell. Physiol. 227: 1157–1167, 2012. © 2011 Wiley Periodicals, Inc.

Ancillary