# CELLULAR COFACTORS IN TRANSCRIPTIONAL ACTIVATION BY TAT

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1993 · $222,170

## Abstract

Human immunodeficiency virus-1 (HIV-1) is the etiological agent of
acquired immune deficiency syndrome (AIDS).  The genome of HIV-1 encodes
several novel regulatory proteins. One of these, Tat, plays a pivotal role
in the life cycle of HIV-1 by regulating HIV-1 mRNA expression. Tat is an
essential protein that increases greatly the expression of genes linked to
HIV-1 long terminal repeat (LTR) by stimulating transcription. It does so
by binding to a structured RNA element, known as TAR RNA, that is present
in the 5' untranslated region of all HIV mRNAs. Studies in vivo in cell
culture model systems suggest that Tat is a unique activator protein that
both increases transcriptional initiation and stabilizes transcriptional
elongation. The precise mechanism of transactivation by Tat remains
unclear; however, the effects of Tat are likely to be mediated through a
direct or indirect interaction with cellular cofactors. A clear
understanding of mechanism of Tat-stimulation may facilitate the
development of specific molecular strategies that interfere with HIV-1
gene expression and mitigate the pathobiological consequences of
infection. A detailed knowledge of the mechanism of transactivation is
likely to emerge from the analysis of a cell free system. At the present
time, little is known about cellular factors that might be involved in
transactivation. In this proposal, a cell free system would be used to
identify and characterize cellular factors that cooperate with Tat in the
stimulation of HIV-1 transcription.  This goal would be accomplished in
three specific aims.  The first is to reconstitute basal HIV-1
transcription by fractionating nuclear extracts and to establish a minimal
system that supports basal but not Tat-stimulated transcription.  The
minimal system will then be used to purify and study cellular proteins
that are required for Tat-stimulated transcription. Thirdly, cellular
proteins that interact with TAR RNA and Tat that are required for Tat-
stimulated transcription will be purified and characterized. The
identification and characterization of cellular activities that play a
role in transactivation by Tat should contribute significantly toward an
understanding of the mechanism of Tat action and may provide avenues of
therapeutic intervention with viral gene expression.

## Key facts

- **NIH application ID:** 3150124
- **Project number:** 1R01AI035656-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** MICHAEL F LASPIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $222,170
- **Award type:** 1
- **Project period:** 1993-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3150124

## Citation

> US National Institutes of Health, RePORTER application 3150124, CELLULAR COFACTORS IN TRANSCRIPTIONAL ACTIVATION BY TAT (1R01AI035656-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3150124. Licensed CC0.

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