Abstract

We propose to continue our studies of the mechanism of transcriptional control in the mammalian cell relying heavily on adenovirus gene expression as a system to study. The major thrust of the work is to understand the manner in which the adenovirus E1A gene product effects transcriptional activation of viral genes and how this reflects similar processes in the uninfected cell. To accomplish this, we will focus on two major aspects of the problem: sequences essential for transcription and regulation and proteins that interact with these sequences. First, we will further define sequences in certain inducible promoters that are essential for the function of the gene. These include the adenovirus E1A enhancer element that are essential for its function. With this information in hand, we will proceed to define proteins that interact with these sequences and thus are presumably participating in the process of transcriptional control. Finally, we will isolate additional cellular genes that are subject to E1A Control.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026765-11
Application #
3274217
Study Section
Molecular Biology Study Section (MBY)
Project Start
1987-06-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Hiebert, S W; Blake, M; Azizkhan, J et al. (1991) Role of E2F transcription factor in E1A-mediated trans activation of cellular genes. J Virol 65:3547-52
Phelps, W C; Bagchi, S; Barnes, J A et al. (1991) Analysis of trans activation by human papillomavirus type 16 E7 and adenovirus 12S E1A suggests a common mechanism. J Virol 65:6922-30
Neill, S D; Nevins, J R (1991) Genetic analysis of the adenovirus E4 6/7 trans activator: interaction with E2F and induction of a stable DNA-protein complex are critical for activity. J Virol 65:5364-73
Chellappan, S P; Hiebert, S; Mudryj, M et al. (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65:1053-61
Mudryj, M; Devoto, S H; Hiebert, S W et al. (1991) Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell 65:1243-53
Rooney, R J; Raychaudhuri, P; Nevins, J R (1990) E4F and ATF, two transcription factors that recognize the same site, can be distinguished both physically and functionally: a role for E4F in E1A trans activation. Mol Cell Biol 10:5138-49
Weigel, R J; Nevins, J R (1990) Adenovirus infection of differentiated F9 cells results in a global shut-off of differentiation-induced gene expression. Nucleic Acids Res 18:6107-12
Raychaudhuri, P; Bagchi, S; Neill, S D et al. (1990) Activation of the E2F transcription factor in adenovirus-infected cells involves E1A-dependent stimulation of DNA-binding activity and induction of cooperative binding mediated by an E4 gene product. J Virol 64:2702-10
Chellappan, S P; Nevins, J R (1990) DNA octamer element can confer E1A trans-activation, and adenovirus infection results in a stimulation of the DNA-binding activity of OTF-1/NFIII factor. Proc Natl Acad Sci U S A 87:5878-82
Bagchi, S; Raychaudhuri, P; Nevins, J R (1990) Adenovirus E1A proteins can dissociate heteromeric complexes involving the E2F transcription factor: a novel mechanism for E1A trans-activation. Cell 62:659-69

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