Differential regulation of c-Jun-dependent transcription by SUMO-specific proteases
Differential regulation of c-Jun-dependent transcription by SUMO-specific proteases
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DOI：
10.1074/jbc.m412185200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Yeh, ETH
中科院分区：
文献类型：
--
作者：
Cheng, JK;Perkins, ND;Yeh, ETH
c-Jun是在调节细胞生长、凋亡、分化和转化中起重要作用的转录因子。c-Jun的转录活性可以通过磷酸化和类小泛素化来调节。也已经表明，c-Jun转录可以由SuPr-1调节，SuPr-1是SUMO特异性蛋白酶2（SENP 2）的可变剪接形式。然而，SuPr-1增强c-Jun转录的能力依赖于早幼粒细胞白血病，但不依赖于SuPr-1的去小泛素化活性。在这里，我们发现SUMO特异性蛋白酶1（SENP 1）也显着增强c-Jun的转录活性。SENP 1对c-Jun转录的作用是独立的sumoylation和磷酸化状态的c-Jun，但严重依赖于SENP 1的去sumoylation活性。我们进一步表明，p300是必不可少的SENP 1，以提高c-Jun依赖的转录，因为SENP 1可以desumoylate的CRD 1结构域的p300，从而释放cRD 1的顺式阻遏p300。因此，两种SUMO特异性蛋白酶通过完全不同的机制调节c-Jun依赖性转录。
c-Jun is a transcription factor that plays an important role in regulating cell growth, apoptosis, differentiation, and transformation. The transcriptional activity of c-Jun can be regulated by both phosphorylation and sumoylation. It has also been shown that c-Jun transcription can be regulated by SuPr-1, an alternatively spliced form of SUMO-specific protease 2 (SENP2). However, the ability of SuPr-1 to enhance c-Jun transcription is dependent on promyelocytic leukemia but is independent of the desumoylation activity of SuPr-1. Here, we show that SUMO-specific protease 1 (SENP1) also markedly enhances the transcription activity of c-Jun. The action of SENP1 on c-Jun transcription is independent of the sumoylation and phosphorylation status of c-Jun but is critically dependent on the desumoylation activity of SENP1. We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300. Thus, two SUMO-specific proteases regulate c-Jun-dependent transcription through entirely different mechanisms.