MECHANISM OF SPECIFICITY IN THE FOS-JUN ONCOPROTEIN HETERODIMER
MECHANISM OF SPECIFICITY IN THE FOS-JUN ONCOPROTEIN HETERODIMER
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DOI：
10.1016/0092-8674(92)90145-3
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发表时间：
1992-02-21
期刊：
影响因子：
64.5
通讯作者：
KIM, PS
中科院分区：
文献类型：
--
作者：
OSHEA, EK;RUTKOWSKI, R;KIM, PS
Fos和Jun是核原癌基因c-fos和c-jun的蛋白产物，优先结合形成异二聚体，该异二聚体结合DNA并调节多种基因的转录以响应促有丝分裂刺激。Fos和Jun都含有一个亮氨酸拉链区。以前的研究表明，亮氨酸拉链的Fos和Jun是必要的，足以介导优先异二聚体的形成。来自Fos和Jun的亮氨酸拉链区域也已知自主折叠，最有可能是双链平行卷曲螺旋。我们在这里表明，从Fos和从六月8个氨基酸是足以介导的GCN 4亮氨酸拉链序列的背景中的优先异二聚体形成。使用pH滴定和氨基酸置换，我们还表明，不稳定的Fos同源二聚体的酸性残基提供了一个主要的热力学驱动力，优先异源二聚体的形成。
Fos and Jun, the protein products of the nuclear proto-oncogenes c-fos and c-jun, associate preferentially to form a heterodimer that binds to DNA and modulates transcription of a wide variety of genes in response to mitogenic stimuli. Both Fos and Jun contain a single leucine zipper region. Previous studies have shown that the leucine zippers of Fos and Jun are necessary and sufficient to mediate preferential heterodimer formation. The leucine zipper regions from Fos and Jun are also known to fold autonomously, most likely as two-stranded, parallel coiled coils. We show here that 8 amino acids from Fos and from Jun are sufficient to mediate preferential heterodimer formation in a background of the GCN4 leucine zipper sequence. Using pH titration and amino acid replacements, we also show that destabilization of the Fos homodimer by acidic residues provides a major thermodynamic driving force for preferential heterodimer formation.