Abstract

Our goal is to study the regulation of gene expression of DNA tumor virus genomes at the molecular level and to use this knowledge to understand the mechanisms of eukaryotic gene expression and virus-host cell interactions. The objectives are to study the transcriptional regulation of adenovirus type 5 early transcriptional region (EII) and to attempt to isolate and characterize the host genes activated by the viral pre-early EIA gene. Transcriptional control elements of the EIIA-late promoter will be identified at the virus level using the linker scanning mutagenesis approach. Functional relationship of the transcriptional control elements of the two DIIA (early and late) promoters and the genetic basis of their differential regulation in viral lytic cycle will be studied using novel mutant viruses. Biochemical approaches such as gel assays for DNA-protein complexes and in vivo assays involving exonuclease III will be employed to identify transcription factors which may interact wih the transcriptional control elements of the two EIIA promoters. Utilizing molecular hybridization and gene cloning techniques, attempts will be made to identify and isolate the host genes activated by the viral pre-early EIA gene.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020156-06
Application #
3129643
Study Section
Virology Study Section (VR)
Project Start
1983-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  Publications

Buchmann, A M; Swaminathan, S; Thimmapaya, B (1998) Regulation of cellular genes in a chromosomal context by the retinoblastoma tumor suppressor protein. Mol Cell Biol 18:4565-76
Swaminathan, S; Rajan, P; Savinova, O et al. (1996) Simian virus 40 large-T bypasses the translational block imposed by the phosphorylation of elF-2 alpha. Virology 219:321-3
Somasundaram, K; Jayaraman, G; Williams, T et al. (1996) Repression of a matrix metalloprotease gene by E1A correlates with its ability to bind to cell type-specific transcription factor AP-2. Proc Natl Acad Sci U S A 93:3088-93
Porras, A; Bennett, J; Howe, A et al. (1996) A novel simian virus 40 early-region domain mediates transactivation of the cyclin A promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays. J Virol 70:6902-8
Manohar, C F; Furtado, M R (1995) Mutational analysis of the adenovirus E2-early promoter in fission yeast Schizosaccharomyces pombe. Biochem Mol Biol Int 37:653-63
Rahman, A; Malhotra, P; Dhar, R et al. (1995) Effect of single-base substitutions in the central domain of virus-associated RNA I on its function. J Virol 69:4299-307
Ghadge, G D; Malhotra, P; Furtado, M R et al. (1994) In vitro analysis of virus-associated RNA I (VAI RNA): inhibition of the double-stranded RNA-activated protein kinase PKR by VAI RNA mutants correlates with the in vivo phenotype and the structural integrity of the central domain. J Virol 68:4137-51
Radosevich, J A; Ghadge, G D; Haines, G K et al. (1994) Characterization of the mouse monoclonal antibody TJ4C4 directed at human p68 kinase. Tumour Biol 15:255-62
Malhotra, P; Manohar, C F; Swaminathan, S et al. (1993) E2F site activates transcription in fission yeast Schizosaccharomyces pombe and binds to a 30-kDa transcription factor. J Biol Chem 268:20392-401
Swaminathan, S; Malhotra, P; Manohar, C F et al. (1993) Activation of a dual adenovirus promoter containing nonconsensus TATA motifs in Schizosaccharomyces pombe: role of TATA sequences in the efficiency of transcription. Nucleic Acids Res 21:2737-46

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