Majello B, De Luca P, Suske G, Lania L
Dipartimento di Genetica, Biologia Generale e Molecolare, Università Federico II, Naples, Italy.
Oncogene. 1995 May 4;10(9):1841-8.
Sp1 and Sp3 are closely related members of a gene family encoding proteins with very similar structural features. The zinc finger DNA binding domains of Sp1 and Sp3 are highly conserved and they bind to GC and GT box with comparable affinities. To begin to delineate the specific roles of these two members of the Sp1-like gene family, here we have analysed the DNA binding specificity and their effects on activation of human c-myc promoter. We found that both proteins bind to the same sites of c-myc promoter, upstream to both the P1 and P2 initiation sites. Cotransfection experiments, in mammalian and insect cells, indicated that Sp1 trans-activate c-myc promoter, whereas Sp3 did not. In addition, enforced expression of Sp3 repressed Sp1-mediated activation of c-myc. Finally, we found that Sp1 and E2F-1/DP-1 cooperatively trans-activate c-myc promoter. In contrast enforced expression of Sp3 fails to repress E2F-1/DP-1-mediated activation.
Sp1和Sp3是一个基因家族中关系密切的成员，该家族编码具有非常相似结构特征的蛋白质。Sp1和Sp3的锌指DNA结合结构域高度保守，它们以相当的亲和力与GC盒和GT盒结合。为了开始阐明Sp1样基因家族这两个成员的具体作用，我们在此分析了它们的DNA结合特异性及其对人c-myc启动子激活的影响。我们发现这两种蛋白质都结合到c-myc启动子的相同位点，位于P1和P2起始位点的上游。在哺乳动物和昆虫细胞中的共转染实验表明，Sp1可反式激活c-myc启动子，而Sp3则不能。此外，Sp3的强制表达可抑制Sp1介导的c-myc激活。最后，我们发现Sp1和E2F-1/DP-1协同反式激活c-myc启动子。相比之下，Sp3的强制表达未能抑制E2F-1/DP-1介导的激活。
