HUMAN PROTOONCOGENE C-JUN ENCODES A DNA-BINDING PROTEIN WITH STRUCTURAL AND FUNCTIONAL-PROPERTIES OF TRANSCRIPTION FACTOR AP-1
HUMAN PROTOONCOGENE C-JUN ENCODES A DNA-BINDING PROTEIN WITH STRUCTURAL AND FUNCTIONAL-PROPERTIES OF TRANSCRIPTION FACTOR AP-1
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DOI：
10.1126/science.2825349
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发表时间：
1987-12-04
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：
BOHMANN, D;BOS, TJ;TJIAN, R
核癌基因产物有可能诱导基因调控的改变，导致癌症的发生。核癌蛋白作用的生化机制仍不清楚。最近，一个癌基因，v-jun，被发现与酵母转录因子GCN 4的DNA结合结构域共享同源性。此外，GCN 4和佛波酯诱导增强子结合蛋白AP-1识别非常相似的DNA序列。人类原癌基因c-jun现已被分离出来，推导的氨基酸序列表明与v-jun有80%以上的同一性。克隆的c-jun在细菌中表达产生了与AP-1具有序列特异性DNA结合特性的蛋白质。针对来自v-jun的两种不同肽产生的抗体与人AP-1特异性反应。此外，纯化的AP-1的部分氨基酸序列显示与c-jun蛋白共同的胰蛋白酶肽。c-jun产物和增强子结合蛋白在结构和功能上的相似性表明AP-1可能由c-jun编码，这些发现表明c-jun的原癌基因产物直接与特定的靶DNA序列相互作用以调节基因表达，因此现在可能鉴定出在c-jun控制下影响细胞生长和肿瘤形成的基因。
Nuclear oncogene products have the potential to induce alterations in gene regulation leading to the genesis of cancer. The biochemical mechanisms by which nuclear oncoproteins act remain unknown. Recently, an oncogene, v-jun, was found to share homology with the DNA binding domain of a yeast transcription factor, GCN4. Furthermore, GCN4 and the phorbol ester-inducible enhancer binding protein, AP-1, recognize very similar DNA sequences. The human proto-oncogene c-jun has now been isolated, and the deduced amino acid sequence indicates more than 80 percent identity with v-jun. Expression of cloned c-jun in bacteria produced a protein with sequence-specific DNA binding properties identical to AP-1. Antibodies raised against two distinct peptides derived from v-jun reacted specifically with human AP-1. In addition, partial amino acid sequence of purified AP-1 revealed tryptic peptides in common with the c-jun protein. The structural and functional similarities between the c-jun product and the enhancer binding protein suggest that AP-1 may be encoded by c-jun. These findings demonstrate that the proto-oncogene product of c-jun interacts directly with specific target DNA sequences to regulate gene expression, and therefore it may now be possible to identify genes under the control of c-jun that affect cell growth and neoplasia.