Giannì Maurizio, Bauer Annie, Garattini Enrico, Chambon Pierre, Rochette-Egly Cécile
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP 163, 67404 Illkirch cedex, France.
EMBO J. 2002 Jul 15;21(14):3760-9. doi: 10.1093/emboj/cdf374.
The nuclear retinoic acid receptor RAR gamma 2 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 RAR gamma 2 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 RAR gamma 2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RAR gamma 2 is linked to transactivation.
核视黄酸受体RARγ2在配体结合后会经历蛋白酶体依赖性降解。在此，我们提供证据表明，介导蛋白酶体降解的结构域与激活转录的结构域重叠，即激活结构域AF-1和AF-2。AF-1结构域通过响应视黄酸（RA）时被p38丝裂原活化蛋白激酶（p38MAPK）磷酸化来介导RARγ2降解。AF-2结构域通过募集属于26S蛋白酶体19S调节亚基的SUG-1发挥作用。通过抑制p38MAPK途径或26S蛋白酶体功能来阻断RARγ2降解会损害其RA诱导的反式激活活性。因此，RARγ2的周转与反式激活相关联。
