The Adenovirus E1A Proteins Induce Apoptosis, which is Inhibited by the E1B 19-kDa and Bcl-2 Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 16; pp. 7742 - 7746
• Main Authors: Rao, Lakshmi, Debbas, Michael, Sabbatini, Peter, Hockenbery, David, Korsmeyer, Stanley, White, Eileen
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.08.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Adenoviridae - genetics; adenovirus; Adenovirus Early Proteins; Adenoviruses; Ageing, cell death; Animals; Apoptosis; Bcl-2 protein; Biological and medical sciences; Cell Death; Cell Line, Transformed; Cell lines; Cell physiology; Cell Transformation, Neoplastic; Cells; Cellular biology; DNA; DNA-Binding Proteins - genetics; E1A protein; E1B protein; Epithelial cells; Fundamental and applied biological sciences. Psychology; Gene Expression; induction; inhibition; Kidney - pathology; Kidney - physiology; Kidney - ultrastructure; Molecular and cellular biology; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Oncogenes; Protein-Tyrosine Kinases - genetics; Proteins; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes; Rats; Rats, Inbred F344; Transfection; transformation; Transformed cell line; Viability; Viruses; Cell proliferation; Adenoviridae; Rat; Rodentia; Cytotoxicity; Cell transformation; Kidney; Virus; Vertebrata; Regulation(control); Mammalia; Cell death; Onc gene; Tumor necrosis factor α
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.16.7742

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 programed 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.