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PMID: 1457005 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 16 ·1992-08-15 ·Pages 7742-6

Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E

Abstract

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.

Related Genes
Bcl-2 E1A E1B
MeSH Terms
Adenoviridae/genetics Adenovirus Early Proteins Animals Cell Death Cell Line, Transformed Cell Transformation, Neoplastic DNA-Binding Proteins/genetics Gene Expression Kidney/pathology,physiology,ultrastructure Oncogene Proteins, Viral/biosynthesis,genetics Oncogenes Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/biosynthesis,genetics Proto-Oncogene Proteins c-bcl-2 Proto-Oncogenes Rats Rats, Inbred F344 Transfection
Chemicals
Adenovirus Early Proteins DNA-Binding Proteins Oncogene Proteins, Viral Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Protein-Tyrosine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rao L
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854.
Debbas M
Sabbatini P
Hockenbery D
Korsmeyer S
White E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.16.7742
Published
1992-08-15
Pages
7742-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49787
Subset
IM
Grants
NCI NIH HHS · CA13106 · United States
NCI NIH HHS · CA53370 · United States
NIGMS NIH HHS · GM08339-02 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.89.16.7742 PMC Full Text View journal details
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