Verma I M, Ransone L J, Visvader J, Sassone-Corsi P, Lamph W W
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138.
Princess Takamatsu Symp. 1989;20:119-26.
Two nuclear oncoproteins, fos and jun (AP-1), cooperate in forming a very stable heterodimeric complex that binds to the AP-1 site with increased affinity. The 'leucine zipper' domain of both fos and jun is necessary for the formation of this heterodimer. Mutations of single residues within the leucine zipper domain had no effect on protein complex formation. However, mutagenesis of the first leucine of the heptad repeat in either fos or jun basic regions and alteration of the spacing between the basic and leucine zipper domains indicate that the basic region of fos has a crucial role in determining the DNA binding affinity of the transcriptional complex. Mutations of the basic amino acids in fos protein prevent binding to TPA (phorbol ester)-responsive element (TRE) in the presence of wild-type jun protein. Thus fos protein appears to be dominant in jun-fos binding to DNA, even though fos alone cannot bind to TRE. Mutants in the basic regions of fos and jun can be exploited as dominant-negative mutants to ablate their normal cellular function.
两种核癌蛋白，即原癌基因Fos和Jun（激活蛋白-1），协同形成一种非常稳定的异二聚体复合物，该复合物以更高的亲和力结合到激活蛋白-1位点。Fos和Jun的“亮氨酸拉链”结构域对于这种异二聚体的形成是必需的。亮氨酸拉链结构域内单个残基的突变对蛋白质复合物的形成没有影响。然而，Fos或Jun碱性区域中七肽重复序列的第一个亮氨酸的诱变以及碱性区域和亮氨酸拉链结构域之间间距的改变表明，Fos的碱性区域在决定转录复合物的DNA结合亲和力方面起着关键作用。在野生型Jun蛋白存在的情况下，Fos蛋白中碱性氨基酸的突变会阻止其与佛波酯（TPA）反应元件（TRE）结合。因此，尽管Fos单独不能与TRE结合，但在Jun-Fos与DNA的结合中Fos蛋白似乎起主导作用。Fos和Jun碱性区域的突变体可作为显性负性突变体来消除它们正常的细胞功能。
