Bohmann D, Bos T J, Admon A, Nishimura T, Vogt P K, Tjian R
Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley, CA 94720.
Science. 1987 Dec 4;238(4832):1386-92. doi: 10.1126/science.2825349.
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.
核致癌基因产物有可能诱导基因调控改变，从而导致癌症的发生。核癌蛋白发挥作用的生化机制仍不清楚。最近，发现一种致癌基因v-jun与酵母转录因子GCN4的DNA结合结构域具有同源性。此外，GCN4和佛波酯诱导的增强子结合蛋白AP-1识别非常相似的DNA序列。现在已经分离出人类原癌基因c-jun，推导的氨基酸序列表明它与v-jun的同源性超过80%。在细菌中克隆c-jun的表达产生了一种具有与AP-1相同的序列特异性DNA结合特性的蛋白质。针对源自v-jun的两种不同肽产生的抗体与人AP-1发生特异性反应。此外，纯化的AP-1的部分氨基酸序列显示出与c-jun蛋白共有的胰蛋白酶肽段。c-jun产物与增强子结合蛋白之间的结构和功能相似性表明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，因此现在有可能鉴定出受c-jun控制的影响细胞生长和肿瘤形成的基因。
