摘要
胸腺嘧啶 DNA glycosylase (TDG ) ，开始 G/T 和 G/U 的修理的酶错配，最近被发现 crucialin 胚胎维持 epigenetic 稳定性并且便于活跃 DNA demethylation 的开发。这里，我们在作为 -catenin/TCFs 建筑群的 transcriptional 激活剂发信号的 Wnt 报导 TDG 的 novelrole。我们 TDG 绑在 thetranscriptional 因素家庭 LEF1/TCFs 并且加强的数据表演 -catenin/TCFs transactivation，当 TDG 弄空压制 Wnt3a-stimulatedreporter 活动或目标基因抄写时。下次，我们显示出那 CBP，已知的激活剂，也为在目标倡导者上形成合作建筑群的 TDG functionthrough 被要求。而且，有在人的冒号 cancertissue 的 TDG 层次的举起，并且 TDG 击倒禁止冒号房间的增长。总的来说，我们的结果表明作为新激活剂， TDG 支持 -catenin/TCFs transactivation 并且机能上地在正规 Wnt 发信号与 CBP 合作。
Thymine DNA glycosylase CrDG）, an enzyme that initiates the repair of G/T and G/U mismatches, has been lately found crucial in em- bryonic development to maintain epigenetic stability and facilitate the active DNA demethylation. Here we report a novel role of TDG in Wnt signaling as a transcriptional coactivator of β-catenin/TCFs complex. Our data show that TDG binds to the transcriptional factor family LEF1/TCFs and potentiates β-catenin/TCFs transactivation, while TDG depletion suppresses Wnt3a-stimulated reporter activity or target gene transcription. Next, we show that CBP, a known coactivator, is also required for TDG function through forming a coopera- tive complex on target promoters. Moreover, there is an elevation of TDG levels in human colon cancer tissue, and knockdown of TDG inhibits proliferation of the colon cells. Overall, our results reveal that TDG, as a new coactivator, promotes β-catenin/TCFs transacti- vation and functionally cooperates with CBP in canonical Wnt signaUng.
