The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.
Cooperation between the adenovirus E1A and E1B oncogenes is required for transformation of primary quiescent rodent cells. Although expression of E1A alone will stimulate cell proliferation sufficient to initiate transformed focus formation, proliferation fails to be sustained and foci degenerate. Coexpression of either the 19-kDa or 55-kDa E1B oncoproteins with E1A permits high-frequency transformation by overcoming this cytotoxic response. Without E1B 19-kDa protein expression, however, transformants remain susceptible to induction of cell death. Rapid loss of viability is coincident with nucleolytic cleavage of DNA in intranucleosomal regions and chromatin condensation, hallmarks of programmed cell death (apoptosis). Furthermore, overexpression of a known suppressor of apoptosis, the Bcl-2 protooncogene, can rescue E1A-induced focus degeneration. Thus E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation. High-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis.
Rao
L
L
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854.
Debbas
M
M
Sabbatini
P
P
Hockenbery
D
D
Korsmeyer
S
S
White
E
E
D000256:Adenoviridae / Q000235:genetics*; D017456:Adenovirus Early Proteins; D000818:Animals; D016923:Cell Death; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D007668:Kidney / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases