Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins.
Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins.
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DOI：
10.1101/gad.3.6.770
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发表时间：
1989-06
影响因子：
10.5
通讯作者：
L. Ransone;J. Visvader;P. Sassone-Corsi;I. Verma
中科院分区：
文献类型：
--
作者：
L. Ransone;J. Visvader;P. Sassone-Corsi;I. Verma
Jun 和 Fos 癌蛋白形成复合物，调节含有 AP-1 结合位点的启动子的转录。 Fos 和 Jun 的“亮氨酸拉链”结构域对于异二聚体的形成是必需的，但特定亮氨酸残基的作用尚不清楚。我们使用位点特异性诱变来检查单个亮氨酸残基对稳定 Fos-Jun 蛋白复合物形成的贡献以及该复合物与 AP-1 位点的结合。 Fos 或 Jun 中单个亮氨酸的突变对蛋白质复合物的形成没有影响。此外，Jun 中两个连续亮氨酸的突变不会干扰异二聚体的形成；然而，就 Fos 而言，两次连续突变导致无法形成异二聚体。尽管七肽重复序列的第一个亮氨酸的诱变对蛋白质复合物的形成没有影响，但 Fos 或 Jun 中的这种突变极大地降低了复合物与 DNA 的亲和力。因此，Fos 和 Jun 都直接有助于异二聚体的 DNA 结合潜力。
Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine the contribution of individual leucine residues to the formation of a stable Fos-Jun protein complex and the binding of this complex to the AP-1 site. Mutation of a single leucine in either Fos or Jun had no effect on protein complex formation. Furthermore, mutations of two consecutive leucines in Jun did not interfere with heterodimer formation; however, in the case of Fos, two consecutive mutations resulted in an inability to form a heterodimer. Although mutagenesis of the first leucine of the heptad repeat had no effect on protein complex formation, this mutation in either Fos or Jun drastically reduced the affinity of the complex for DNA. Thus, both Fos and Jun contribute directly to the DNA-binding potential of the heterodimer.