Shtrichman R, Kleinberger T
Unit of Molecular Microbiology, The B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
J Virol. 1998 Apr;72(4):2975-82. doi: 10.1128/JVI.72.4.2975-2982.1998.
Adenovirus type 5 E4 open reading frame 4 (E4orf4) protein has been previously shown to counteract transactivation of the junB and c-fos genes by cyclic AMP plus E1A protein and to interact with protein phosphatase 2A (PP2A). Here, we show that the wild-type E4orf4 protein induces apoptosis in the E1A-expressing 293 cells, in NIH 3T3 cells transformed with v-Ras, and in the lung carcinoma cell line H1299. The induction of apoptosis is not accompanied by enhanced levels of p53 in 293 cells and occurs in the absence of p53 in H1299 cells, indicating involvement of a p53-independent pathway. A mutant E4orf4 protein that had lost the ability to induce apoptosis also lost its ability to bind PP2A. We suggest that E4orf4 antagonizes continuous signals to proliferate, like those given by E1A or v-Ras, and that the conflicting signals lead to the induction of cell death.
5型腺病毒E4开放阅读框4（E4orf4）蛋白先前已被证明可通过环磷酸腺苷加E1A蛋白来对抗junB和c-fos基因的反式激活，并与蛋白磷酸酶2A（PP2A）相互作用。在此，我们表明野生型E4orf4蛋白可在表达E1A的293细胞、用v-Ras转化的NIH 3T3细胞以及肺癌细胞系H1299中诱导凋亡。凋亡的诱导在293细胞中并不伴随着p53水平的升高，且在H1299细胞中p53缺失的情况下发生，这表明涉及一条不依赖p53的途径。一种已丧失诱导凋亡能力的突变型E4orf4蛋白也丧失了与PP2A结合的能力。我们认为E4orf4拮抗持续的增殖信号，如E1A或v-Ras所发出的信号，并且这些相互冲突的信号导致细胞死亡的诱导。
