Synergistic, p160 coactivator-dependent enhancement of estrogen receptor function by CARM1 and p300
Synergistic, p160 coactivator-dependent enhancement of estrogen receptor function by CARM1 and p300
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DOI：
10.1074/jbc.m005459200
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发表时间：
2000-12-29
影响因子：
4.8
通讯作者：
Stallcup, MR
中科院分区：
文献类型：
--
作者：
Chen, DG;Huang, SM;Stallcup, MR
p160辅激活因子家族成员p160共激活因子（类固醇受体共激活因子-I（SRC-1）、糖皮质激素受体相互作用蛋白I（GRIP 1）和甲状腺和视黄酸受体的激活因子（ACTR））介导核受体的转录激活。在被核受体募集到启动子后，p160共激活因子通过两个C末端激活结构域AD 1和AD 2传递激活信号，AD 1是相关辅激活因子cAMP-反应元件结合蛋白结合蛋白（CBP）和p300的结合位点，而AD 2结合另一辅激活因子，辅激活因子相关精氨酸甲基转移酶1（CARM 1），一种蛋白质-精氨酸甲基转移酶。目前的研究探讨了GRIP 1，CARM 1和p300在瞬时转染试验中的合作功能和机制关系，它们增强了雌激素受体（ER）激活报告基因转录的能力。p300和CARM 1的共激活因子功能依赖于GRIP 1的共表达。同时共表达的所有三个辅激活剂引起的协同增强ER功能。GRIP 1的AD 1结构域的缺失消除了p300增强ER活性的能力，但对CARM 1介导的刺激没有影响。相反，当GRIP 1的AD 2结构域被删除时，p300仍然通过突变的GRIP 1刺激ER功能，但CARM 1不能这样做。因此，p300与AD 1的结合和CARM 1与AD 2的结合都是它们各自的共激活因子功能和它们的协同作用所需要的。此外，CARM 1和p300通过GRIP 1的不同激活结构域独立发挥作用，它们的协同作用表明它们通过不同的互补结构域增强转录。机制等
Members of the p160 coactivator family (steroid receptor coactivator-l (SRC-1), glucocorticoid receptor interacting protein 1 (GRIP1), and activator of thyroid and retinoic acid receptors (ACTR)) mediate transcriptional activation by nuclear receptors, After being recruited to the promoter by nuclear receptors, the p160 coactivator transmits the activating signal via two C-terminal activation domains, AD1 and AD2, AD1 is a binding site for the related coactivators cAMP-response element binding protein binding protein (CBP) and p300, whereas AD2 binds to another coactivator, coactivator-associated arginine methyltransferase 1 (CARM1), a protein-arginine methyltransferase. The current study explored the cooperative functional and mechanistic relationships among GRIP1, CARM1, and p300 in transient transfection assays, where they enhanced the ability of the estrogen receptor (ER) to activate transcription of a reporter gene. The coactivator functions of p300 and CARM1 depended on the co-expression of GRIP1. Simultaneous co-expression of all three coactivators caused a synergistic enhancement of ER function. Deletion of the AD1 domain of GRIP1 abolished the ability of p300 to potentiate ER activity but had no effect on CARM1-mediated stimulation. In contrast, when the AD2 domain of GRIP1 was deleted, p300 still stimulated ER function through the mutant GRIP1, but CARM1 failed to do so. Thus, both binding of p300 to AD1 and binding of CARM1 to AD2 are required for their respective coactivator functions and for their synergy. Furthermore, CARM1 and p300 function independently through different activating domains of GRIP1, and their synergy suggests that they enhance transcription by different, complementary. mechanisms.