Gao M, Morgan I, Vogt P K
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Cancer Res. 1996 Sep 15;56(18):4229-35.
We compared the ability of cellular and viral Jun (c-Jun and v-Jun) to transactivate target genes. c-Jun and v-Jun bind specifically to 12-O-tetradecanoylphorbol-13-acetate responsive elements [TREs, also called activator protein 1 (AP-1) motifs]. However, whereas c-Jun activates TRE-controlled promoters, v-Jun represses them. Cotransfection of the two Jun proteins reduces c-Jun-dependent transactivation. The expression of the endogenous c-jun gene, regulated through a promoter-proximal AP-1-binding site, is repressed in v-Jun-transformed chicken embryo fibroblasts. It is suggested that an M(r) 18,000 v-Jun peptide prominent in v-Jun-transformed cells acts as a transdominant-negative regulator of AP-1 activity and of c-jun expression. In contrast to the results with TRE sites, both v-Jun and c-Jun activate transcription through the human T-cell leukemia virus type I 21-bp repeat which contains a sequence homologous to the cyclic AMP responsive element. However, full-length Jun proteins bind to this site only with low affinity, and binding of the truncated v-Jun was barely detectable. These observations show that the oncogenic viral form of Jun differs from the cellular version in promoter preference and on certain promoters acts as an antagonist to c-Jun.
我们比较了细胞型和病毒型Jun（c-Jun和v-Jun）激活靶基因的能力。c-Jun和v-Jun特异性结合12-氧-十四烷酰佛波醇-13-乙酸酯反应元件[TREs，也称为激活蛋白1（AP-1）基序]。然而，c-Jun可激活TRE控制的启动子，而v-Jun则抑制它们。两种Jun蛋白共转染会降低c-Jun依赖的反式激活作用。通过启动子近端AP-1结合位点调控的内源性c-jun基因的表达，在v-Jun转化的鸡胚成纤维细胞中受到抑制。提示在v-Jun转化细胞中显著存在的一种相对分子质量为18,000的v-Jun肽，可作为AP-1活性和c-jun表达的反式显性负调控因子。与TRE位点的结果相反，v-Jun和c-Jun均可通过人I型T细胞白血病病毒21 bp重复序列激活转录，该重复序列含有与环磷酸腺苷反应元件同源的序列。然而，全长Jun蛋白仅以低亲和力结合该位点，截短的v-Jun的结合几乎检测不到。这些观察结果表明，Jun的致癌病毒形式在启动子偏好方面与细胞形式不同，并且在某些启动子上可作为c-Jun的拮抗剂。
