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

doi:10.1002/jcp.22836

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 journal › Article › peer-review

50 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 language	English
Pages (from-to)	1157-1167
Number of pages	11
Journal	Journal of Cellular Physiology
Volume	227
Issue number	3
DOIs	https://doi.org/10.1002/jcp.22836
Publication status	Published - 2012 Mar
Externally published	Yes

Keywords

Apoptosis
Bcl-XL
Clusterin

ASJC Scopus subject areas

Physiology
Clinical Biochemistry
Cell Biology

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10.1002/jcp.22836

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Kim, N., Yoo, J. C., Han, J. Y., Hwang, E. M., Kim, Y. S., Jeong, E. Y., Sun, C. H., Yi, G. S., Roh, G. S., Kim, H. J., Kang, S. S., Cho, G. J., Park, J. Y., & Choi, W. S. (2012). Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain. Journal of Cellular Physiology, 227(3), 1157-1167. https://doi.org/10.1002/jcp.22836

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

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.",

keywords = "Apoptosis, Bcl-XL, Clusterin",

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

year = "2012",

month = mar,

doi = "10.1002/jcp.22836",

language = "English",

volume = "227",

pages = "1157--1167",

journal = "Journal of Cellular Physiology",

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T1 - Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain

AU - Kim, Nayoung

AU - Yoo, Jae Cheal

AU - Han, Jae Yoon

AU - Hwang, Eun Mi

AU - Kim, Yoon Sook

AU - Jeong, Eun Young

AU - Sun, Choong Hyun

AU - Yi, Gwan Su

AU - Roh, Gu Seob

AU - Kim, Hyun Joon

AU - Kang, Sang Soo

AU - Cho, Gyeong Jae

AU - Park, Jae Yong

AU - Choi, Wan Sung

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bcl-XL

KW - Clusterin

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DO - 10.1002/jcp.22836

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VL - 227

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EP - 1167

JO - Journal of Cellular Physiology

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IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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