Collaborator of stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates stat6-dependent gene transcription
Collaborator of stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates stat6-dependent gene transcription
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DOI：
10.1074/jbc.m611283200
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发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Boothby, Mark
中科院分区：
文献类型：
--
作者：
Goenka, Shreevrat;Cho, Sung Hoon;Boothby, Mark
转录因子Stat 6在白细胞介素-4依赖性基因激活中起关键作用。为了介导这一功能，Stat 6招募典型的转录辅激活因子，包括组蛋白乙酰转移酶CREB结合蛋白和NCoA-1以及其他蛋白质，如p100辅因子。然而，关于Stat 6增强子复合物的成分仍有很多未知之处，调节Stat 6依赖性基因激活的确切分子事件也尚未完全了解。最近，我们发现了一种新的辅因子CoaSt 6（Stat 6的合作者），它与Stat 6相关并增强其转录活性。序列同源性将CoaSt 6置于聚（ADP-核糖基）聚合酶（PARP）样蛋白的超家族中。我们已经证明PARP酶活性与CoaSt 6相关，CoaSt 6的这种功能可以将ADP-核糖附加到自身和p100上。此外，我们发现CoaSt 6的催化失活突变体不能增强Stat 6介导的测试启动子的转录。与这些发现一致，PARP活性的化学抑制在体内阻断了靶启动子的白细胞介素-4依赖性转录。两者合计，我们已经确定了CoaSt 6相关的PARP活性，并提供了证据的作用，聚（ADP核糖基）化的STAT介导的转录反应，涉及一种新的PARP。
The transcription factor Stat6 plays a critical role in interleukin-4-dependent gene activation. To mediate this function, Stat6 recruits canonical transcriptional co-activators including the histone acetyl transferases CREB-binding protein and NCoA-1 and other proteins such as a p100 co-factor. However, much remains unknown regarding the constituents of Stat6 enhancer complexes, and the exact molecular events that modulate Stat6-dependent gene activation are not fully understood. Recently, we identified a novel co-factor, CoaSt6 (collaborator of Stat6), which associates with Stat6 and enhances its transcriptional activity. Sequence homologies place CoaSt6 in a superfamily of poly(ADP-ribosyl) polymerase (PARP)-like proteins. We have demonstrated here that PARP enzymatic activity is associated with CoaSt6, and this function of CoaSt6 can append ADP-ribose to itself and p100. Further, we show that a catalytically inactive mutant of CoaSt6 was unable to enhance Stat6-mediated transcription of a test promoter. Consistent with these findings, chemical inhibition of PARP activity blocked interleukin-4-dependent transcription from target promoters in vivo. Taken together, we have identified a CoaSt6-associated PARP activity and provided evidence for a role of poly(ADP ribosyl)ation in Stat-mediated transcriptional responses involving a novel PARP.