LEUCINE REPEATS AND AN ADJACENT DNA-BINDING DOMAIN MEDIATE THE FORMATION OF FUNCTIONAL CFOS-CJUN HETERODIMERS
LEUCINE REPEATS AND AN ADJACENT DNA-BINDING DOMAIN MEDIATE THE FORMATION OF FUNCTIONAL CFOS-CJUN HETERODIMERS
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DOI：
10.1126/science.2494701
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发表时间：
1989-03-31
期刊：
影响因子：
56.9
通讯作者：
TJIAN, R
中科院分区：
文献类型：
--
作者：
TURNER, R;TJIAN, R
AP-1家族的增强子结合因子包括细胞Fos（cFos）和细胞Jun（cJun）蛋白的复合物，这一发现在肿瘤发生和转录调控之间建立了直接和重要的联系。体外合成的同源二聚体cJun蛋白能够选择性地结合AP-1识别位点，而cFos多肽则不能。当共翻译时，cFos和cJun蛋白可以与AP-1/cJun的DNA结合特性形成稳定的异二聚体复合物。相关蛋白Jun B和vJun也能够与cFos形成DNA结合复合物。cFos蛋白的定向诱变揭示了亮氨酸重复结构是结合cJun所必需的，其方式与“亮氨酸拉链”的拟议功能一致。“一个新的结构域相邻，但不同的，亮氨酸重复的cFos是需要的DNA结合cFos-cJun异二聚体。因此，实验证据表明，亮氨酸重复序列可以介导异源蛋白质之间的复合物的形成，并促进进一步了解两个原癌基因产物的功能的分子机制。
The discovery that the AP-1 family of enhancer binding factors includes a complex of the cellular Fos (cFos) and cellular Jun (cJun) proteins established a direct and important link between oncogenesis and transcriptional regulation. Homodimeric cJun protein synthesized in vitro is capable of binding selectively to AP-1 recognition sites, whereas the cFos polypeptide is not. When cotranslated, the cFos and cJun proteins can form a stable, heterodimeric complex with the DNA binding properties of AP-1/cJun. The related proteins Jun B and vJun are also able to form DNA binding complexes with cFos. Directed mutagenesis of the cFos protein reveals that a leucine repeat structure is required for binding to cJun, in a manner consistent with the proposed function of the "leucine zipper." A novel domain adjacent to, but distinct from, the leucine repeat of cFos is required for DNA binding by cFos-cJun heterodimers. Thus experimental evidence is presented that leucine repeats can mediate complex formation between heterologous proteins and that promotes further understanding of the molecular mechanisms underlying the function of two proto-oncogene products.