Cook J L, Krantz C K, Routes B A
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13985-90. doi: 10.1073/pnas.93.24.13985.
The mechanism by which the adenoviral (Ad) E1A oncogene induces cellular susceptibility to lysis by killer lymphocytes involves interactions between its first exon and different second-exon accessory regions. Mutational analysis showed that two first-exon regions--one in the N terminus and one in the conserved region 1 (CR1) domain--are necessary for this activity. E1A complex formation with cellular p300 protein through these first-exon-encoded regions correlated with induction of the cytolytic susceptible phenotype but was only effective in the context of E1A second-exon expression. An E1A first-exon deletion that prevented p300 binding eliminated both oncoprotein-induced cytolytic susceptibility and rejection of transfected sarcoma cells by immunocompetent animals. These results suggest that the E1A oncogene induces cytolytic susceptibility and tumor rejection by interactions with cellular proteins of the p300 family that affect transcription of genes involved in the cellular response to injury inflicted by host killer cells.
腺病毒（Ad）E1A癌基因诱导细胞对杀伤淋巴细胞裂解产生易感性的机制涉及其第一个外显子与不同的第二个外显子辅助区域之间的相互作用。突变分析表明，两个第一个外显子区域——一个在N末端，一个在保守区域1（CR1）结构域——对于这种活性是必需的。通过这些第一个外显子编码区域与细胞p300蛋白形成E1A复合物与溶细胞易感表型的诱导相关，但仅在E1A第二个外显子表达的情况下有效。一个阻止p300结合的E1A第一个外显子缺失消除了癌蛋白诱导的溶细胞易感性以及免疫活性动物对转染肉瘤细胞的排斥。这些结果表明，E1A癌基因通过与p300家族的细胞蛋白相互作用诱导溶细胞易感性和肿瘤排斥，这些细胞蛋白影响参与细胞对宿主杀伤细胞造成损伤的反应的基因的转录。
