Cheng Jinke, Perkins Neil D, Yeh Edward T H
Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Biol Chem. 2005 Apr 15;280(15):14492-8. doi: 10.1074/jbc.M412185200. Epub 2005 Feb 8.
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.
c-Jun是一种转录因子，在调节细胞生长、凋亡、分化和转化过程中发挥重要作用。c-Jun的转录活性可通过磷酸化和SUMO化进行调节。研究还表明，c-Jun转录可受SUMO特异性蛋白酶2（SENP2）的可变剪接形式SuPr-1调控。然而，SuPr-1增强c-Jun转录的能力依赖于早幼粒细胞白血病，且与SuPr-1的去SUMO化活性无关。在此，我们表明SUMO特异性蛋白酶1（SENP1）也能显著增强c-Jun的转录活性。SENP1对c-Jun转录的作用与c-Jun的SUMO化和磷酸化状态无关，但关键依赖于SENP1的去SUMO化活性。我们进一步表明，p300对于SENP1增强c-Jun依赖性转录至关重要，因为SENP1可使p300的CRD1结构域去SUMO化，从而解除CRD1对p300的顺式抑制。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。
