Functional similarity between adenovirus e1b 19k gene and bcl2 oncogene - mutant complementation and suppression of cell-death induced by DNA-damaging agents.

Adenovirus mutants defective in a 19 kD protein (19K gene) encoded by the early region E1B induce DNA fragmentation in a manner similar to the internucleosomal DNA fragmentation observed during programmed cell death (apoptosis) induced by a number of chemical, physical and biological stimuli. Zn++ ions effectively suppressed DNA fragmentation induced by a 19K mutant consistent with their inhibition of DNA fragmentation during apoptosis. Since the cellular proto-oncogene Bcl2 has been shown to suppress DNA fragmentation and the resulting programmed cell death, we have carried out a functional complementation analysis to determine whether the E1B 19 kD protein is functionally similar to the Bcl2 protein. Our results indicate that the DNA fragmentation induced by the 19K mutant can be efficiently suppressed by stable expression of human Bcl2 protein. Further, the 19 kD and Bcl2 proteins also function similarly to suppress DNA fragmentation and cell death induced by the DNA damaging agents cisplatin and UV.