Transcriptional intermediary factor 1α mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor interacting protein 1 nuclear receptor coactivators
Transcriptional intermediary factor 1α mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor interacting protein 1 nuclear receptor coactivators
复制标题
DOI：
10.1210/me.2005-0393
复制
发表时间：
2006-06-01
影响因子：
--
通讯作者：
Stallcup, Michael R.
中科院分区：
文献类型：
--
作者：
Teyssier, Catherine;Ou, Chen-Yin;Stallcup, Michael R.
在以前的研究中，转录中间因子1 α（TIF 1 α）被确定为核受体（NR）的直接结合伴侣和潜在的转录共激活因子，但其过表达抑制，而不是增强，由NR的转录激活。在这里，我们表明TIF 1 α结合并增强了共激活因子相关精氨酸甲基转移酶1（CARM 1）的C-末端激活结构域（AD）和糖皮质激素受体相互作用蛋白1（GRIP 1）的N-末端AD的功能。此外，尽管TIF 1 α本身具有很少或没有NR共激活因子活性，但它与GRIP 1和CARM 1协同作用以增强NR介导的转录。内源性TIF 1 α表达的抑制降低了GRIP 1 N-末端结构域而不是CARM 1 C-末端结构域的转录激活，表明TIF 1 α可能对介导前者的活性比后者更重要。内源性TIF 1 α水平的降低也损害了雄激素受体内源性靶基因的雄激素依赖性诱导。最后，TIF 1 α与GRIP 1 N-末端和CARM 1 C-末端结构域形成三元复合物。因此，我们得出结论，TIF 1 α与NR共激活剂GRIP 1和CARM 1通过与它们形成稳定的三元复合物并增强它们中的一个或两个的AD功能而合作。
In previous studies transcriptional intermediary factor 1 alpha (TIF1 alpha) was identified as a direct binding partner and potential transcriptional coactivator for nuclear receptors (NRs) but its overexpression inhibited, rather than enhanced, transcriptional activation by NRs. Here we show that TIF1 alpha bound to and enhanced the function of the C- terminal activation domain ( AD) of coactivator associated arginine methyltransferase 1 ( CARM1) and the N- terminal AD of glucocorticoid receptor-interacting protein 1 (GRIP1). Furthermore, although TIF1 alpha had little or no NR coactivator activity by itself, it cooperated synergistically with GRIP1 and CARM1 to enhance NR-mediated transcription. Inhibition of endogenous TIF1 alpha expression reduced transcriptional activation by the GRIP1 N- terminal domain but not by the CARM1 C- terminal domain, suggesting that TIF1 alpha may be more important for mediating the activity of the former than the latter. Reduction of endogenous TIF1 alpha levels also compromised the androgen-dependent induction of an endogenous target gene of the androgen receptor. Finally, TIF1 alpha formed a ternary complex with the GRIP1N-terminal and CARM1 C- terminal domains. Thus, we conclude that TIF1 alpha cooperates with NR coactivators GRIP1 and CARM1 by forming a stable ternary complex with them and enhancing the AD function of one or both of them.