Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in transformed cells.
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.
Shtrichman
R
R
Unit of Molecular Microbiology, The B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Kleinberger
T
T
D016475:3T3 Cells; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D006801:Humans; D051379:Mice; D009154:Mutation; D016366:Open Reading Frames; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D054648:Protein Phosphatase 2; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017504:Adenovirus E4 Proteins; D016159:Tumor Suppressor Protein p53; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2