Role of TRIM33 in Wnt signaling during mesendoderm differentiation
Role of TRIM33 in Wnt signaling during mesendoderm differentiation
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TRIM33 在中内胚层分化过程中 Wnt 信号传导中的作用
DOI：
10.1007/s11427-017-9129-3
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发表时间：
2017-10-01
影响因子：
9.1
通讯作者：
Xi, Qiaoran
中科院分区：
文献类型：
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作者：
Xia, Xiaojie;Zuo, Feifei;Xi, Qiaoran
TRIM 33是转录辅助因子转录中间因子1（TIF 1）家族的成员，在小鼠胚胎发育早期的中内胚层分化过程中通过其PHD-Bromo盒介导转化生长因子-β（TGF-β）信号传导。然而，TRIM 33 RING结构域在胚胎分化中的作用尚不清楚。在这里，我们报告说，TRIM 33介导的Wnt信号通过直接调节一个特定的子集的Wnt靶基因的表达，这一行动是独立于其RING结构域。我们发现TRIM 33与β-连环蛋白相互作用，β-连环蛋白是小鼠胚胎干细胞（mESC）中Wnt信号传导的核心参与者。与先前在癌细胞系中的报道相反，RING结构域似乎不起β-连环蛋白的E3连接酶的作用，因为TRIM 33的敲除或过表达对mESC中的β-连环蛋白蛋白水平都没有影响。此外，我们表明，虽然TRIM 33似乎是通过报告基因测定Wnt信号转导，TRIM 33的损失显着损害的Wnt靶基因的一个子集，包括Mixl 1，在Wnt信号依赖性的方式表达。总之，我们的研究结果表明，TRIM 33调节Wnt信号转导独立于其RING结构域的E3连接酶活性，用于mESC中的β-连环蛋白。
Tripartite motif 33 (TRIM33), a member of the transcription intermediate factor 1 (TIF1) family of transcription cofactors, mediates transforming growth factor-beta (TGF-beta) signaling through its PHD-Bromo cassette in mesendoderm differentiation during early mouse embryonic development. However, the role of the TRIM33 RING domain in embryonic differentiation is less clear. Here, we report that TRIM33 mediates Wnt signaling by directly regulating the expression of a specific subset of Wnt target genes, and this action is independent of its RING domain. We show that TRIM33 interacts with beta-catenin, a central player in Wnt signaling in mouse embryonic stem cells (mESCs). In contrast to previous reports in cancer cell lines, the RING domain does not appear to function as the E3 ligase for beta-catenin, since neither knockout nor overexpression of TRIM33 had an effect on beta-catenin protein levels in mESCs. Furthermore, we show that although TRIM33 seems to be dispensable for Wnt signaling through a reporter assay, loss of TRIM33 significantly impairs the expression of a subset of Wnt target genes, including Mixl1, in a Wnt signaling-dependent manner. Together, our results indicate that TRIM33 regulates Wnt signaling independent of the E3 ligase activity of its RING domain for beta-catenin in mESCs.