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PMID: 2975754 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The amino-terminal region of the adenovirus serotype 5 E1a protein performs two separate functions when expressed in primary baby rat kidney cells.

Molecular and cellular biology ·Vol. 8 ·No. 9 ·1988-09-00 ·Pages 3882-90

Smith DH, Ziff EB

Abstract

Adenovirus serotype 5 E1a proteins immortalize primary cells and in cooperation with products of a second oncogene, such as adenovirus serotype 5 E1b or EJ ras, produce full transformation. E1a also activates transcription of specific viral and cellular promoters, represses enhancer-dependent genes, and induces cellular DNA synthesis in quiescent cells. Comparison of different adenovirus serotypes has identified three conserved regions in the E1a protein sequence. We have analyzed E1a mutants with deletions-linker insertions in or preceding the first conserved region, region 1 (amino acids 40 through 77 of adenovirus serotype 5 E1a). E1a mutants which have in-frame deletions-substitutions in region 1 or pre-region 1 sequences were reconstructed into adenovirus to yield a total of 14 mutant viruses. All the mutant viruses showed wild-type growth in HeLa cells, confirming that region 1 is nonessential in these cells. However, we show that region 1 provides two distinct functions in infected primary rodent cells. One function is essential for induction of cell DNA synthesis, and the other is essential for focus formation. In addition, our results are consistent with a requirement for the DNA induction function in focus formation.

MeSH Terms
Adenovirus Early Proteins Adenoviruses, Human/classification,genetics,growth & development Amino Acid Sequence Animals Antigens, Viral, Tumor/genetics Cell Line Cell Transformation, Neoplastic Cells, Cultured DNA Replication Genetic Vectors HeLa Cells/metabolism Humans Kidney Mice Molecular Sequence Data Mutation Oncogene Proteins, Viral/genetics,physiology Rats Serotyping
Chemicals
Adenovirus Early Proteins Antigens, Viral, Tumor Oncogene Proteins, Viral
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Smith D H
Department of Biochemistry, New York University Medical Center, New York 10016.
Ziff E B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.8.9.3882-3890.1988
Published
1988-09-00
Pages
3882-90
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC365447
Subset
IM
Grants
NIGMS NIH HHS · GM 30760 · United States
External Links
PubMed source DOI: 10.1128/mcb.8.9.3882-3890.1988 PMC Full Text Free Full Text View journal details
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