Minc E, de Coppet P, Masson P, Thiery L, Dutertre S, Amor-Guéret M, Jaulin C
Institut d'Oncologie Cellulaire et Moléculaire Humaine, 129, Route de Stalingrad, F-93000 Bobigny, France.
J Biol Chem. 1999 Jan 1;274(1):503-9. doi: 10.1074/jbc.274.1.503.
Human copper-zinc superoxide dismutase (Cu,Zn-SOD) participates in the control of reactive oxygen intermediate intracellular concentration. In this study, we show that phorbol 12-myristate 13-acetate (PMA) increases Cu,Zn-SOD mRNA expression within 30 min. The sequence between nucleotides -71 and -29 is essential for both basal and PMA-induced gene expression. This region includes an Sp1-binding site that is also recognized by a possible Sp1-like protein and by Egr-1 in a PMA-inducible manner. Egr-1 and two splicing variants of the Egr-related protein WT1 were able to transactivate the SOD1 promoter in co-transfection experiments. Sp1 and the possible Sp1-like proteins bind to two overlapping, but distinct sequences. However, Egr-1 and Sp1 seem to interact with two sites that are either identical or very close to each other. None of these sites fit the consensus sequences previously reported for these proteins. Analysis of various mutants of the SOD1 proximal promoter revealed that the region that binds Sp1 and Egr-1 is required for both basal and Egr-1-driven expression. Interplay between different members of the Sp1 family, Egr-1, and different splicing variants of WT1 in the SOD1 proximal promoter may provide clues about the physiological function of Cu,Zn-SOD.
人类铜锌超氧化物歧化酶（Cu,Zn-SOD）参与细胞内活性氧中间产物浓度的调控。在本研究中，我们发现佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）在30分钟内可增加Cu,Zn-SOD mRNA的表达。核苷酸-71至-29之间的序列对于基础和PMA诱导的基因表达均至关重要。该区域包含一个Sp1结合位点，该位点也可被一种可能的Sp1样蛋白以及Egr-1以PMA诱导的方式识别。在共转染实验中，Egr-1和Egr相关蛋白WT1的两个剪接变体能够激活SOD1启动子。Sp1和可能的Sp1样蛋白与两个重叠但不同的序列结合。然而，Egr-1和Sp1似乎与两个相同或非常接近的位点相互作用。这些位点均不符合先前报道的这些蛋白的共有序列。对SOD1近端启动子各种突变体的分析表明，结合Sp1和Egr-1的区域对于基础表达和Egr-1驱动的表达均是必需的。SOD1近端启动子中Sp1家族不同成员、Egr-1和WT1不同剪接变体之间的相互作用可能为Cu,Zn-SOD的生理功能提供线索。
