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腺病毒转化的19-kD T抗原具有增强子依赖性反式激活功能,并可解除由病毒和细胞基因介导的增强子抑制作用。

Adenovirus transforming 19-kD T antigen has an enhancer-dependent trans-activation function and relieves enhancer repression mediated by viral and cellular genes.

作者信息

Yoshida K, Venkatesh L, Kuppuswamy M, Chinnadurai G

机构信息

Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110.

出版信息

Genes Dev. 1987 Sep;1(7):645-58. doi: 10.1101/gad.1.7.645.

Abstract

The adenovirus E1b region codes for two major tumor antigens of 19 kD and 55 kD, which are important for cell transformation. Our results indicate that the 19-kD T antigen possesses two enhancer-regulatory functions. It can trans-activate enhancer-linked promoters and relieve enhancer repression mediated by viral and cellular repressors. The 19-kD activation function enhances expression from different promoters linked to SV40, Py, Ela, and immunoglobulin heavy-chain enhancers. Enhancer activation by the 19-kD protein appears to be cell type-specific, since the heavy-chain and SV40 enhancers were not trans-activated in myeloma cells whereas the same enhancers were trans-activated in fibroblasts. The 19-kD enhancer activation function appears to be dominant over the enhancer repression function of E1a, since in cells expressing the 19-kD protein there is no significant repression despite a large increase in E1a expression. The 19-kD T antigen activates the Py enhancer in undifferentiated F9 cells indicating that the activation function of E1b masks enhancer repression by an "E1a-like" cellular gene product. The enhancer activation function of the 19-kD T antigen may be important for cell transformation and cell differentiation.

摘要

腺病毒E1b区域编码两种主要的肿瘤抗原,分别为19kD和55kD,它们对细胞转化很重要。我们的结果表明,19kD的T抗原具有两种增强子调节功能。它可以反式激活与增强子相连的启动子,并解除由病毒和细胞阻遏物介导的增强子抑制。19kD的激活功能增强了与SV40、Py、Ela和免疫球蛋白重链增强子相连的不同启动子的表达。19kD蛋白对增强子的激活似乎具有细胞类型特异性,因为重链和SV40增强子在骨髓瘤细胞中未被反式激活,而在成纤维细胞中相同的增强子被反式激活。19kD的增强子激活功能似乎比E1a的增强子抑制功能更具优势,因为在表达19kD蛋白的细胞中,尽管E1a表达大幅增加,但没有明显的抑制作用。19kD的T抗原在未分化的F9细胞中激活Py增强子,这表明E1b的激活功能掩盖了由一种“E1a样”细胞基因产物介导的增强子抑制。19kD的T抗原的增强子激活功能可能对细胞转化和细胞分化很重要。

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