Role of the adenovirus E1B 19,000-dalton tumor antigen in regulating early gene expression

White, E., Denton, A., Stillman, B. (1988) Role of the adenovirus E1B 19,000-dalton tumor antigen in regulating early gene expression. Journal of Virology, 62 (9). pp. 3445-54. ISSN 0022-538X

URL: http://www.ncbi.nlm.nih.gov/pubmed/2969984

Abstract

Mutations in the adenovirus gene encoding the E1B 19-kilodalton protein (the 19K protein) result in pleiotropic phenotypes that affect the host cell and virus growth. Examination of viral gene expression in HeLa cells infected with E1B 19K mutant viruses revealed synthesis and accumulation of E1A proteins to higher steady-state levels than those proteins synthesized during infection with the wild-type virus. As a consequence of elevated E1A levels, another early gene product, the 72K DNA-binding protein, accumulated earlier in mutant-infected cells. In a 12S E1A cDNA virus background, E1B 19K gene mutations had a more profound effect. Larger amounts of the 12S E1A product were present in E1B mutant-infected cells. A deletion mutation that eliminated expression of the 19K protein was also responsible for a 200-fold increased plaque-forming efficiency of the 12S cDNA virus in HeLa cells and an increased rate of virus production. Therefore, the E1B 19K tumor antigen may function to down-regulate virus replication by repressing E1A-dependent gene transcription. Eliminating expression of the E1A 13S and 12S gene products by substitution of an E1A 9S cDNA gene, however, uncovered a stimulatory effect of the E1B 19K protein on early gene expression and virus replication. An E1A 9S virus with a wild-type gene encoding the E1B 19K protein displayed increased early gene transcription, synthesized more 72K DNA-binding protein, and replicated more efficiently than an E1A 9S virus containing a mutation that eliminated expression of the 19K protein. Therefore, the E1B 19K protein has both positive and negative effects on early gene expression and virus replication. In the presence of functional E1A gene products, the 19K protein repressed E1A-dependent gene expression, but in the absence of E1A, the 19K protein stimulated viral gene expression and DNA synthesis. This raises the possibility that the E1B 19K protein functions to repress transcription by modifying the activity of the E1A proteins. Independent of E1A, however, the E1B 19K protein can increase viral gene expression and DNA synthesis, which then leads to increased virus replication.

Item Type: Paper
Uncontrolled Keywords: Adenoviridae genetics growth & development immunology physiology Adenovirus Early Proteins Antigens Viral Tumor biosynthesis genetics DNA Viral analysis DNA-Binding Proteins analysis Gene Expression Regulation Hela Cells Humans Immunoassay Mutation Nucleic Acid Hybridization Oncogene Proteins Viral biosynthesis genetics RNA Viral analysis Transcription Genetic Virus Replication
Subjects: bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
organism description > virus
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date Deposited: 17 Feb 2012 19:30
Last Modified: 20 Jun 2017 20:28
PMCID: PMC253469
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25138

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