The AF-1 and AF-2 domains of RARγ2 and RXRα cooperate for triggering the transactivation and the degradation of RARγ2/RXRα heterodimers
The AF-1 and AF-2 domains of RARγ2 and RXRα cooperate for triggering the transactivation and the degradation of RARγ2/RXRα heterodimers
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DOI：
10.1074/jbc.m304952200
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发表时间：
2003-09-05
影响因子：
4.8
通讯作者：
Rochette-Egly, C
中科院分区：
文献类型：
--
作者：
Gianní, M;Tarrade, A;Rochette-Egly, C
在真核细胞中，配体的 RARgamma2/RXRα 异二聚体激活视黄酸 (RA) 靶基因的转录，然后通过泛素-蛋白酶体途径降解。在这项研究中，我们剖析了 RARgamma2 和 RXRalpha 伙伴以及它们各自的 AF-1 和 AF-2 结构域在反式激活和降解过程中的作用。 RARgamma2 是启动转录及其在配体结合后自身降解的“引擎”。受体的降解和反式激活都需要 AF-2 结构域的完整性和 AF-1 结构域的磷酸化。删除整个 AF-1 结构域不会损害这些过程，但会通过 RXRalpha 将受体转向其他蛋白水解途径。相比之下，RXRalpha 仅发挥调节作用，通过其 AF-2 结构域和磷酸化 AF-1 结构域与 RARgamma2 配合，参与 RARgamma2/RXRalpha 异二聚体的转录活性和降解。我们的结果强调，每个异二聚体伙伴的 AF-1 和 AF-2 结构域相互合作，并且这种合作与转录和降解过程相关。
In eukaryotic cells, liganded RARgamma2/RXRalpha heterodimers activate the transcription of retinoic acid ( RA) target genes and then are degraded through the ubiquitin-proteasome pathway. In this study, we dissected the role of the RARgamma2 and RXRalpha partners as well as of their respective AF-1 and AF-2 domains in the processes of transactivation and degradation. RARgamma2 is the "engine" initiating transcription and its own degradation subsequent to ligand binding. Integrity of its AF-2 domain and phosphorylation of its AF-1 domain are required for both the degradation and the transactivation of the receptor. Deletion of the whole AF-1 domain does not impair these processes but shifts the receptor toward other proteolytic pathways through RXRalpha. In contrast, RXRalpha plays only a modulatory role, cooperating with RARgamma2 through its AF-2 domain and its phosphorylated AF-1 domain in both the transcription activity and the degradation of the RARgamma2/RXRalpha heterodimers. Our results underline that the AF-1 and AF-2 domains of each heterodimer partner cooperate with one other and that this cooperation is relevant for both the transcription and degradation processes.