Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway
Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway
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DOI：
10.1101/gad.1461706
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发表时间：
2006-11-01
影响因子：
10.5
通讯作者：
Kumar, Rakesh
中科院分区：
文献类型：
--
作者：
Zhang, Hao;Singh, Rajesh R.;Kumar, Rakesh
在这里，我们发现MTA3的表达抑制了处女和怀孕小鼠转基因乳腺的导管分支。MTA3也抑制Wnt4通路，因此，这些发现与Wnt4缺失小鼠的表型变化相似。MTA3抑制Wnt4转录和Wnt4分泌，抑制乳腺上皮细胞中wnt靶基因。因此，内源性MTA3的敲低刺激Wnt4表达和Wnt细胞靶点。MTA3-NuRD（核小体重塑和去乙酰化酶）复合物以hdac依赖的方式与Wnt4染色质物理相互作用，导致Wnt4基因和Wnt4依赖的形态发生受到抑制。这些发现表明MTA3是乳腺上皮细胞中Wnt4的上游生理性抑制因子。
Here we show that expression of MTA3 inhibits ductal branching in virgin and pregnant murine transgenic mammary glands. MTA3 also suppresses the Wnt4 pathway and, thus, these findings parallel phenotypic changes in Wnt4-null mice. MTA3 represses Wnt4 transcription and Wnt4 secretion, inhibiting Wnt-target genes in mammary epithelial cells. Accordingly, knockdown of endogenous MTA3 stimulates Wnt4 expression and Wnt cellular targets. The MTA3-NuRD (nucleosome remodeling and deacetylase) complex physically interacts with the Wnt4 chromatin in an HDAC-dependent manner, leading to suppression of the Wnt4 gene and Wnt4-dependent morphogenesis. These findings identify MTA3 as an upstream physiologic repressor of Wnt4 in mammary epithelial cells.