Clusterin, a novel modulator of TGF-β signaling, is involved in Smad2/3 stability

被引：50

作者：

Lee, Kwan-Bok ^{[1
]}

Jeon, Jun-Ho ^{[2
]}

Choi, Inpyo ^{[3
]}

Kwon, O-Yu ^{[4
]}

Yu, Kweon ^{[5
]}

You, Kwan-Hee ^{[1
]}

机构：

[1] Chungnam Natl Univ, Sch Biosci & Biotechnol, Taejon 305764, South Korea

[2] Sookmyung Womens Univ, Dept Life Sci, Res Ctr Womens Dis, Seoul, South Korea

[3] Korea Res Inst Biosci & Biotechnol, Ctr Stem Cell, Taejon, South Korea

[4] Chungnam Natl Univ, Coll Med, Dept Anat, Taejon 305764, South Korea

[5] Korea Res Inst Biosci & Biotechnol, Ctr Regenerat Med, Taejon, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 366卷 / 04期

关键词：

clusterin; TGF-beta; Smad2; Smad3;

D O I：

10.1016/j.bbrc.2007.12.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. It is known that CLU interacts with TGF-beta type 11 receptor (T beta R11). However, the relationship of CLU and TGF-beta signaling is unclear. Here we present that CLU is a novel modulator of TGF-beta signaling by regulating Smad2/3 proteins. Overexpression of CLU enhanced TGF-beta-induced transcriptional activity and increased the amount of Smad2/3 proteins, while CLU siRNA repressed TGF-beta-induced transcriptional activity and decreased the amount of Smad2/3 proteins in Hep3B cells. We also found that CLU was involved in Smad2/3 stability at the protein level. These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：905 / 909

页数：5

共 29 条

[1]

BLASCHUK O, 1983, J BIOL CHEM, V258, P7714

[2] A tale of two proteins:: Differential roles and regulation of Smad2 and Smad3 in TGF-β signaling [J].

Brown, Kimberly A. ;

Pietenpol, Jennifer A. ;

Moses, Harold L. .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2007, 101 (01) :9-33

[3]

ChoiMiura NH, 1996, NEUROBIOL AGING, V17, P717

[4] MURINE CLUSTERIN - MOLECULAR-CLONING AND MESSENGER-RNA LOCALIZATION OF A GENE ASSOCIATED WITH EPITHELIAL DIFFERENTIATION PROCESSES DURING EMBRYOGENESIS [J].

FRENCH, LE ;

CHONN, A ;

DUCREST, D ;

BAUMANN, B ;

BELIN, D ;

WOHLWEND, A ;

KISS, JZ ;

SAPPINO, AP ;

TSCHOPP, J ;

SCHIFFERLI, JA .

JOURNAL OF CELL BIOLOGY, 1993, 122 (05) :1119-1130

[5] HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IκB and β-catenin [J].

Fuchs, SY ;

Chen, A ;

Xiong, Y ;

Pan, ZQ ;

Ronai, Z .

ONCOGENE, 1999, 18 (12) :2039-2046

[6] Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins [J].

Fukuchi, M ;

Imamura, T ;

Chiba, T ;

Ebisawa, T ;

Kawabata, M ;

Tanaka, K ;

Miyazono, K .

MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (05) :1431-1443

[7] Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1 [J].

Hatakeyama, S ;

Kitagawa, M ;

Nakayama, K ;

Shirane, M ;

Matsumoto, M ;

Hattori, K ;

Higashi, H ;

Nakano, H ;

Okumura, K ;

Onoé, K ;

Good, RA ;

Nakayama, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3859-3863

[8] Clusterin regulates drug-resistance in melanoma cells [J].

Hoeller, C ;

Pratscher, B ;

Thallinger, C ;

Winter, D ;

Fink, D ;

Kovacic, B ;

Sexl, V ;

Wacheck, V ;

Gleave, ME ;

Pehamberger, H ;

Jansen, B .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 124 (06) :1300-1307

[9] Dys-regulation of Clusterin in human hepatoma is not associated with tumorigenesis but is secondary to cell response to external tresses [J].

Hsieh, SY ;

Chen, WY ;

Shih, TC ;

Yeh, JY ;

Jeng, JT .

MOLECULAR CARCINOGENESIS, 2005, 43 (02) :100-107

[10] Effects of clusterin overexpression on TNF alpha- and TGF beta-mediated death of L929 cells [J].

Humphreys, D ;

Hochgrebe, TT ;

EasterbrookSmith, SB ;

Tenniswood, MP ;

Wilson, MR .

BIOCHEMISTRY, 1997, 36 (49) :15233-15243

← 1 2 3 →