Acetylation of β-catenin by p300 regulates β-catenin-Tcf4 interaction
Acetylation of β-catenin by p300 regulates β-catenin-Tcf4 interaction
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DOI：
10.1128/mcb.24.8.3404-3414.2004
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发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Neuveut, C
中科院分区：
文献类型：
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作者：
Lévy, L;Wei, Y;Neuveut, C
赖氨酸乙酰化调节非组蛋白调节蛋白的活性，并在细胞基因转录调控中起关键作用。在这项研究中，我们表明，转录辅激活因子p300乙酰化β-连环蛋白在赖氨酸345，位于臂重复序列6，在体外和体内。该残基的乙酰化增加了β-连环蛋白对Tcf 4的亲和力，并且细胞中与Tcf 4结合的β-连环蛋白库显着富集了乙酰化形式。我们证明了p300的乙酰转移酶活性是有效激活β-连环蛋白/Tcf 4介导的转录所必需的，并且K345 R突变严重降低了p300和β-连环蛋白之间的合作，这意味着β-连环蛋白的乙酰化在p300对β-连环蛋白的共激活中起作用。有趣的是，β-连环蛋白的乙酰化对β-连环蛋白与雄激素受体的结合有相反的负面影响。我们的数据表明，β-连环蛋白在臂6域的乙酰化调节β-连环蛋白的转录活性，通过差异调节其亲和力Tcf 4和雄激素受体。因此，我们的研究结果描述了一种新的机制，p300可能调节β-连环蛋白的转录活性。
Lysine acetylation modulates the activities of nonhistone regulatory proteins and plays a critical role in the regulation of cellular gene transcription. In this study, we showed that the transcriptional coactivator p300 acetylated beta-catenin at lysine 345, located in arm repeat 6, in vitro and in vivo. Acetylation of this residue increased the affinity of beta-catenin for Tcf4, and the cellular Tcf4-bound pool of beta-catenin was significantly enriched in acetylated form. We demonstrated that the acetyltransferase activity of p300 was required for efficient activation of transcription mediated by beta-catenin/Tcf4 and that the cooperation between p300 and P-catenin was severely reduced by the K345R mutation, implying that acetylation of eta-catenin plays a part in the coactivation of beta-catenin by p300. Interestingly, acetylation of beta-catenin had opposite, negative effects on the binding of beta-catenin to the androgen receptor. Our data suggest that acetylation of beta-catenin in the arm 6 domain regulates beta-catenin transcriptional activity by differentially modulating its affinity for Tcf4 and the androgen receptor. Thus, our results describe a new mechanism by which p300 might regulate beta-catenin transcriptional activity.