Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARγ degradation and transactivation
Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARγ degradation and transactivation
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DOI：
10.1093/emboj/cdf374
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发表时间：
2002-07-15
期刊：
影响因子：
11.4
通讯作者：
Rochette-Egly, C
中科院分区：
文献类型：
--
作者：
Giannì, M;Bauer, A;Rochette-Egly, C
核视黄酸受体RAR γ 2在配体结合后经历蛋白酶体依赖性降解。在这里，我们提供的证据表明，信号蛋白酶体介导的降解的结构域与那些激活转录，即激活结构域AF-1和AF-2重叠。AF-1结构域通过p38MAPK磷酸化RARgamma2降解来响应RA。AF-2结构域通过SUG-1的募集起作用，SUG-1属于26S蛋白酶体的19S调节亚基。通过抑制p38 MAPK通路或26 S蛋白酶体功能来阻断RAR γ 2降解会损害其RA诱导的反式激活活性。因此，RAR γ 2的周转与反式激活有关。
The nuclear retinoic acid receptor RARgamma2 undergoes proteasome-dependent degradation upon ligand binding. Here we provide evidence that the domains that signal proteasome-mediated degradation overlap with those that activate transcription, i.e. the activation domains AF-1 and AF-2. The AF-1 domain signals RARgamma2 degradation through its phosphorylation by p38MAPK in response to RA. The AF-2 domain acts via the recruitment of SUG-1, which belongs to the 19S regulatory subunit of the 26S proteasome. Blocking RARgamma2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RARgamma2 is linked to transactivation.