Smad2 functions as a co-activator of canonical Wnt/β-catenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300

被引：63

作者：

Hirota, Morihisa ^{[1
,2
]}

Watanabe, Kazuhide ^{[1
,2
]}

Hamada, Shin ^{[1
]}

Sun, Youping ^{[1
,5
]}

Strizzi, Luigi ^{[1
,3
]}

Mancino, Mario ^{[1
,6
]}

Nagaoka, Tadahiro ^{[1
]}

Gonzales, Monica ^{[1
]}

Seno, Masaharu ^{[4
]}

Bianco, Caterina ^{[1
]}

Salomon, David S. ^{[1
]}

机构：

[1] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Canc Res Ctr,Natl Inst Hlth, Bethesda, MD 20892 USA

[2] Tohoku Univ, Div Gastroenterol, Sendai, Miyagi 9810933, Japan

[3] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA

[4] Okayama Univ, Lab Nanobiotechnol, Dept Med & Bioengn Sci, Okayama, Japan

[5] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[6] Oncol Res Ctr, Mercogliano, AV, Italy

来源：

CELLULAR SIGNALLING | 2008年 / 20卷 / 09期

关键词：

activin; beta-catenin; smads; Tcf/Lef; TGF-beta; Wnt;

D O I：

10.1016/j.cellsig.2008.05.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

Both canonical Wnt/beta-catenin and TGF beta/Smad signaling pathways coordinately regulate pattern formation during embryogenesis as well as tumor progression. Evidence of cross-talk between these two pathways has been reported. Here we demonstrated that the Activin-like kinase 4 (Alk4)/Smad2 pathway facilitates the transcriptional activity of the oncogenic Wnt/beta-catenin/Tcf4 pathway through a novel Smad4-independent mechanism. Upon activation, Smad2 physically interacted with Tcf4, beta-catenin and the co-activator p300 to enhance transcriptional activity of beta-catenin/Tcf4 through the histone acetyltransferase activity of p300. Transactivation by Smad2 was independent of a Smad-binding element (SBE) and Smad4. Indeed, the enhancement of beta-catenin/Tcf4 transcriptional activity by activated Smad2 was negatively regulated by the presence of Smad4. Moreover, a tumor-derived missense mutant of Smad2, lacking the ability to bind to Smad4 was still able to enhance the Tcf4 transcriptional reporter in the presence of p-catenin and Tcf4. Our findings suggest that Smad2 may function as an activator of canonical Wnt/beta-catenin/Tcf4 signaling through a SBE/Smad4-independent pathway. Published by Elsevier Inc.

引用

页码：1632 / 1641

页数：10

共 55 条

[1]

Attisano L, 1996, MOL CELL BIOL, V16, P1066

[2]

Duel nature of TGF-β signaling:: tumor suppressor vs. tumor promoter [J].