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PMID: 2524598 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The cellular transcription factor E2f requires viral E1A and E4 gene products for increased DNA-binding activity and functions to stimulate adenovirus E2A gene expression.

Journal of virology ·Vol. 63 ·No. 6 ·1989-06-00 ·Pages 2709-17

Babiss LE

Abstract

Whereas a wide variety of cellular proteins interact with the cis-regulatory elements of the adenovirus E1A and E2A genes, only the DNA-binding activity of the cellular E2f factor is modulated by viral early-gene expression. An analysis of cellular E2f protein levels and adenovirus early-gene expression in a panel of independently cloned virus-transformed rodent cell lines and in virus-infected rodent cells has established that both the E1A 289-amino-acid (289R) protein and a yet-to-be-defined E4 gene product are required for maximal E2f DNA-binding activity. To distinguish between the multiple roles the E1A protein could serve in this process, the E2f DNA-binding activity was determined in a virus-transformed cell line which contains a conditional-lethal mutation affecting the 289R protein. Since E4 gene expression was not altered by the incubation conditions, the observation of reduced cellular E2f activity at the nonpermissive temperature suggests a direct role for the E1A 289R protein in E2f activation. When a virus containing a deletion in the E4 gene was introduced into cell lines which can complement the E4 gene defect, a correlation between high cellular E2f levels and increased rates of E2A gene transcription was observed. A time course analysis of the viral infection revealed that E2f functions catalytically to stimulate viral E2A gene transcription. These observations have led to several hypotheses concerning possible mechanisms by which elevated E2A gene expression, which leads to cytotoxicity, might be avoided in the transformed cell.

MeSH Terms
Adenovirus Early Proteins Adenoviruses, Human/genetics Animals Cell Line, Transformed Clone Cells DNA-Binding Proteins/genetics Gene Expression Regulation HeLa Cells Humans Oncogene Proteins, Viral/biosynthesis,genetics Transcription Factors/genetics Transcription, Genetic
Chemicals
Adenovirus Early Proteins DNA-Binding Proteins Oncogene Proteins, Viral Transcription Factors
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Babiss L E
Rockefeller University, New York, New York 10021-6399.
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.63.6.2709-2717.1989
Published
1989-06-00
Pages
2709-17
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC250763
Subset
IM
Grants
NCI NIH HHS · CA48707-01 · United States
External Links
PubMed source DOI: 10.1128/JVI.63.6.2709-2717.1989 PMC Full Text View journal details
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