Transcription Factor Zic2 Inhibits Wnt/β-Catenin Protein Signaling

被引：67

作者：

Pourebrahim, Rasoul ^{[1
]}

Houtmeyers, Rob ^{[1
]}

Ghogomu, Stephen ^{[3
]}

Janssens, Sylvie ^{[5
,6
]}

Thelie, Aurore ^{[3
]}

Hong Thi Tran ^{[5
,6
]}

Langenberg, Tobias ^{[4
]}

Vleminckx, Kris ^{[5
,6
]}

Bellefroid, Eric ^{[3
]}

Cassiman, Jean-Jacques ^{[1
]}

Tejpar, Sabine ^{[1
,2
]}

机构：

[1] Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium

[2] Katholieke Univ Leuven, Dept Gastroenterol, B-3000 Louvain, Belgium

[3] Univ Libre Bruxelles, Lab Embryol Mol, B-6041 Gosselies, Belgium

[4] VRC, B-3000 Louvain, Belgium

[5] Univ Ghent, Dept Mol Biomed Res, VIB, B-9052 Ghent, Belgium

[6] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 43期

关键词：

EMBRYONIC STEM-CELLS; BETA-CATENIN; POLY(ADP-RIBOSE) POLYMERASE-1; XENOPUS-LAEVIS; WNT; GENE; ACTIVATION; EXPRESSION; MUTATIONS; HINDBRAIN;

D O I：

10.1074/jbc.M111.242826

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：

The Zic transcription factors play critical roles during embryonic development. Mutations in the ZIC2 gene are associated with human holoprosencephaly, but the etiology is still unclear. Here, we report a novel function for ZIC2 as a regulator of beta-catenin.TCF4-mediated transcription. We show that ZIC2 can bind directly to the DNA-binding high mobility group box of TCF4 via its zinc finger domain and inhibit the transcriptional activity of the beta-catenin.TCF4 complex. However, the binding of TCF4 to DNA was not affected by ZIC2. Zic2 RNA injection completely inhibited beta-catenin-induced axis duplication in Xenopus embryos and strongly blocked the ability of beta-catenin to induce expression of known Wnt targets in animal caps. Moreover, Zic2 knockdown in transgenic Xenopus Wnt reporter embryos led to ectopic Wnt signaling activity mainly at the midbrain-hindbrain boundary. Together, our results demonstrate a previously unknown role for ZIC2 as a transcriptional regulator of the beta-catenin.TCF4 complex.

引用

页码：37732 / 37740

页数：9

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