Trans-dominant negative mutants of Fos and Jun.
Trans-dominant negative mutants of Fos and Jun.
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Fos 和 Jun 的反式显性负突变体。
DOI：
10.1073/pnas.87.10.3806
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发表时间：
1990
影响因子：
11.1
通讯作者：
Verma,IM
中科院分区：
文献类型：
--
作者：
Ransone,LJ;Visvader,J;Wamsley,P;Verma,IM
Jun 和 Fos 核癌蛋白形成复合物，调节含有激活蛋白 AP-1 结合位点的启动子的转录。 Fos 和 Jun 的亮氨酸拉链和碱性区结构域对于形成与 DNA 结合的异二聚体是必需的。 Fos 或 Jun 基本区域的相互突变可以影响异二聚体与 DNA 的结合，这意味着结合位点是对称的。 Jun 的 DNA 结合突变体表现出对 Fos 的亲和力增加，并且能够抑制野生型 Fos-Jun DNA 结合活性。相比之下，Fos 基本结构域中的突变（阻止与 Jun 相关的 DNA 结合）不会显着降低野生型异二聚体与 DNA 结合的能力。这些显性失活突变体在体内具有功能，可用于研究 Fos 和 Jun 在正常细胞和转化细胞中的作用。
Jun and Fos nuclear oncoproteins form a complex that regulates transcription from promoters containing activator protein AP-1 binding sites. The leucine-zipper and basic-region domains of both Fos and Jun are necessary for formation of the heterodimer that binds to DNA. Reciprocal mutations in the basic region of Fos or Jun can influence the binding of the heterodimer to DNA, implying a symmetrical binding site. DNA-binding mutants of Jun exhibit increased affinity for Fos and are capable of suppressing wild-type Fos-Jun DNA-binding activity. In contrast, mutations in the basic domain of Fos, which prevent binding to DNA in association with Jun, do not significantly diminish the ability of the wild-type heterodimer to bind to DNA. These dominant negative mutants are functional in vivo and can be exploited to study the role of Fos and Jun in normal and transformed cells.