Control of CBP co-activating activity by arginine methylation
Control of CBP co-activating activity by arginine methylation
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DOI：
10.1093/emboj/cdf548
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发表时间：
2002-10-15
期刊：
影响因子：
11.4
通讯作者：
Vandel, L
中科院分区：
文献类型：
--
作者：
Chevillard-Briet, M;Trouche, D;Vandel, L
组蛋白乙酰转移酶 CREB 结合蛋白 (CBP) 和相关的 p300 蛋白作为关键转录共激活因子发挥作用；在多个途径中。在核受体转录激活的情况下，配体促进 p160 家族共激活因子（例如 GRIP-1）的募集。随后，p160 共激活剂招募其他共激活剂；通过两个激活域 AD1 和 AD2。 AD1 结合 CBP 或 p300，而 AD2 已被证明可以通过招募精氨酸甲基转移酶 CARM1 来激活转录。最近，CBP 的 KIX 结构域已被证明在体外被 CARM1 甲基化。在这里，我们报道了 CBP 的另一个结构域在体外和体内被 CARM1 在保守的精氨酸残基上特异性甲基化。我们还提供了功能证据，表明 CARM1 甲基化的精氨酸残基在 GRIP-1 依赖性转录激活和激素诱导的基因激活中发挥着关键作用。总而言之，我们的数据提供了强有力的证据，表明精氨酸甲基化是调节共激活因子转录活性的重要机制。
The histone acetyltransferases CREB binding protein (CBP) and the related p300 protein function as key transcriptional co-activators; in multiple pathways. In the case of transcriptional activation by nuclear receptors, ligand promotes the recruitment of co-activators of the p160 family, such as GRIP-1. Subsequently, the p160 co-activators recruit other co-activators; via two activation domains, AD1 and AD2. AD1 binds CBP or p300, whereas AD2 has been shown to activate transcription through the recruitment of the arginine methyltransferase CARM1. Recently, the KIX domain of CBP has been shown to be methylated by CARM1 in vitro. Here, we report that another domain of CBP is specifically methylated by CARM1 on conserved arginine residues in vitro and in vivo. We also provide functional evidence that arginine residues methylated by CARM1 play a critical role in GRIP-1-dependent transcriptional activation and in hormone-induced gene activation. Altogether, our data provide strong evidence that arginine methylation represents an important mechanism for modulating co-activator transcriptional activity.