# ORGANIZATION AND EXPRESSION OF DNA TUMOR VIRUS GENOMES

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1993 · $198,621

## Abstract

This proposal focuses on the transcriptional regulation of an adenovirus
(Ad) early promoter (E2-early) which transcribes a region of the viral
genome that encodes a 72 kD single stranded DNA binding protein, an 80 kD
precursor terminal protein and the 140 kD DNA polymerase all of which are
vital for virus growth. Transcriptional regulation of the E2-early
promoter involves protein-protein interactions between multiple cellular
transcription factors and several virus-encoded transactivators.  During
the previous grant period, we have defined the cis-acting sequence
elements of this promoter within the context of the viral chromosome,
identified several cellular transcription factors that bind to these
sequence elements and the role of the virus-encoded transactivators that
regulate transcription of this promoter.  We propose to continue these
studies and use genetic and biochemical approaches to elucidate the
mechanisms by which this promoter is regulated by the cellular
transcription factors and the virus-encoded transactivators.  We have the
following specific aims:

Recent results show that in addition to ElA, the E2 early promoter is
transactivated by one of the Ad early region 4 polypeptides (E4 6/7) and
the single stranded DNA binding protein.  We will use genetic and
biochemical approaches to determine the mechanism of transactivation of
the E2-early promoter by these gene products.

We will attempt to clone the cDNA that encodes the cellular transcription
factor E2F which plays a critical role in E2-early promoter
transcription.  The E2F also plays an important role in cell cycle
regulation and binds to retinoblastoma susceptibility gene (RB) product,
an RB related protein pl07, cycline A and cdk2 kinase.  A cDNA clone of
E2F is a valuable reagent for a number of studies which include studies
of structure-functional relationship of E2F, and its role in cell cycle
regulation.

We will dissect the in vivo DNA-protein interactions of the E2-early
promoter in basal and virus induced transcription with the ligation
mediated PCR amplification approach.  In this study, we will use a series
of Ad mutants that we previously constructed, which contain mutations in
different transcription factor binding sites of the E2-early promoter.

## Key facts

- **NIH application ID:** 3129640
- **Project number:** 2R01AI020156-09A2
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** BAYAR THIMMAPAYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $198,621
- **Award type:** 2
- **Project period:** 1983-08-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129640

## Citation

> US National Institutes of Health, RePORTER application 3129640, ORGANIZATION AND EXPRESSION OF DNA TUMOR VIRUS GENOMES (2R01AI020156-09A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129640. Licensed CC0.

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