Envelope-dependent transactivation by the retroviral oncoprotein v-Rel is required for efficient malignant transformation of chicken spleen cells.
Envelope-dependent transactivation by the retroviral oncoprotein v-Rel is required for efficient malignant transformation of chicken spleen cells.
复制标题
逆转录病毒癌蛋白 v-Rel 的包膜依赖性反式激活是鸡脾细胞有效恶性转化所必需的。
DOI：
10.1038/sj.onc.1203651
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Gilmore,TD
中科院分区：
文献类型：
--
作者：
Epinat,JC;Dvorin,EL;Gilmore,TD
逆转录病毒癌蛋白v-Rel是在其N末端具有11个辅助病毒衍生的包膜（Env）氨基酸（aa）的嵌合蛋白。在v-Rel的这些N-末端Env aa内，与Rev-A辅助病毒Env相比，存在三个aa取代。这些aa取代先前已显示赋予v-Rel许多独特的性质，包括增加的转化和反式激活能力。在这项研究中，我们分析了序列要求的Env aa的影响几个属性的v-Rel。氨基酸3和9处的Phe残基对于V-Rel的N-末端反式激活功能是关键的，并且对几种Env突变体的分析表明，反式激活能力与V-Rel的转化能力平行。取代保守的氨基酸，如亮氨酸和酪氨酸，苯丙氨酸3和9是耐受的反式激活鸡胚成纤维细胞和鸡脾细胞的转化。相比之下，在v-Rel的N末端的10个Phe残基的取代不能实现反式激活，表明围绕Phe-3和Phe-9的不同结构对于v-Rel功能是必需的。我们还表明，将v-Rel Env aa添加到人c-Rel的N末端可以使其能够激活转录。总之，这些结果表明，位置3和9处的Phe残基已被选择用于其通过增加其激活转录的能力来增强v-Rel的致癌性的能力。
The retroviral oncoprotein v-Rel is a chimeric protein that has 11 helper virus-derived Envelope (Env) amino acids (aa) at its N terminus. Within these N-terminal Env aa of v-Rel there are three aa substitutions compared to the Rev-A helper virus Env. These aa substitutions have previously been shown to impart a number of unique properties onto v-Rel, including increased transforming and transactivating ability. In this study, we have analysed the sequence requirements for the Env aa to influence several properties of v-Rel. Phe residues at aa 3 and 9 are critical for an N-terminal transactivation function of v-Rel, and the analysis of several Env mutants demonstrates that transactivation ability parallels the transforming ability of v-Rel. Substitutions of conservative aa, such as leucine and tyrosine, for Phe 3 and 9 are tolerated for transactivation in chicken embryo fibroblasts and for transformation of chicken spleen cells. In contrast, the substitution of 10 Phe residues at the N terminus of v-Rel does not enable transactivation, indicating that a distinct structure surrounding Phe-3 and Phe-9 is essential for v-Rel function. We also show that the addition of the v-Rel Env aa to the N terminus of human c-Rel can enable it to activate transcription. Taken together, these results indicate that Phe residues at positions 3 and 9 have been selected for their ability to enhance the oncogenicity of v-Rel by increasing its ability to activate transcription.