Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains
Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains
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DOI：
10.1128/mcb.11.7.3624-3632.1991
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发表时间：
1991-07
影响因子：
5.3
通讯作者：
C. Abate;D. Luk;T. Curran
中科院分区：
文献类型：
--
作者：
C. Abate;D. Luk;T. Curran
由原癌基因c-fos和c-jun（分别为Fos和Jun）编码的蛋白质形成异二聚体复合物，其通过与称为激活蛋白1（AP-1）结合位点的DNA调节元件相互作用来调节转录。Fos和Jun是相关转录因子家族的成员，其通过亮氨酸拉链结构二聚化，并通过在富含碱性氨基酸的每个蛋白质的区域之间形成的二分结构域与DNA相互作用。在这里，我们已经定义了Fos-Jun异二聚体中有助于体外转录功能的其他结构域。虽然DNA结合特异性是由亮氨酸拉链和碱性区域介导的，但Jun也含有富含脯氨酸和谷氨酰胺的区域，其作为辅助DNA结合结构域发挥作用，但不直接参与转录激活。体外转录刺激与Fos中的两个区域和Jun中的单个N-末端激活结构域相关。这些激活子区域能够独立操作;然而，它们似乎在异二聚体复合物中协同发挥作用。这些结构域的活性受到Fos和Jun中抑制体外转录的抑制性区域的调节。在异源二聚体的背景下，Jun激活结构域是转录刺激的主要贡献者，Fos中的抑制区域是体外转录抑制的主要贡献者。潜在地，抑制结构域可以在体内发挥调节功能。因此，Fos-Jun异二聚体的转录调控是由多个激活因子和调控结构域的复杂整合引起的。
The proteins encoded by the proto-oncogenes c-fos and c-jun (Fos and Jun, respectively) form a heterodimeric complex that regulates transcription by interacting with the DNA-regulatory element known as the activator protein 1 (AP-1) binding site. Fos and Jun are members of a family of related transcription factors that dimerize via a leucine zipper structure and interact with DNA through a bipartite domain formed between regions of each protein that are rich in basic amino acids. Here we have defined other domains in the Fos-Jun heterodimer that contribute to transcriptional function in vitro. Although DNA-binding specificity is mediated by the leucine zipper and basic regions, Jun also contains a proline- and glutamine-rich region that functions as an ancillary DNA-binding domain but does not contribute directly to transcriptional activation. Transcriptional stimulation in vitro was associated with two regions in Fos and a single N-terminal activation domain in Jun. These activator regions were capable of operating independently; however, they appear to function cooperatively in the heterodimeric complex. The activity of these domains was modulated by inhibitory regions in Fos and Jun that repressed transcription in vitro. In the context of the heterodimer, the Jun activation domain was the major contributor to transcriptional stimulation and the inhibitory regions in Fos were the major contributors to transcriptional repression in vitro. Potentially, the inhibitory domains could serve a regulatory function in vivo. Thus, transcriptional regulation by the Fos-Jun heterodimer results from a complex integration of multiple activator and regulatory domains.