# REGULATION OF TRANSCRIPTION BY A TUMOR PROMOTER

> **NIH NIH R01** · ST. JOHN'S UNIVERSITY · 1989 · $151,413

## Abstract

The long term objective of the work is to understand at the
molecular level how tumor promoters in particular the phorbol
ester 12otetradecanoylphorbol13acetate (TPA), interact
with cell and virus genes to produce a transformed phenotype in
cells exposed to an initiating carcinogenic stimulus.  This proposal
continues to test the general hypothesis that TPA stimulates the
transcription of specific genes by altering the activity and/or
specificity of RNA polymerase II, and to examine the mechanism
of this effect.  The proposed experiments will attempt to identify
components of the regulatory pathway as well as targets
associated directly with the process of transcription.  Successful
conclusion of the experiments will provide an in vitro test for the
regulation of cloned cell sequences responsive to TPA in vivo, and
will lay the groundwork for complete in vitro reconstruction of a
biologically important transmembrane signaling pathway.

The proposed experiments will characterize the requirements for
stimulation of in vitro transcription of the type 5 human
adenovirus (Ad5) immediate early gene (E1A) by activated
endogenous protein kinase C in whole cell extracts and by purified
Ckinase in reconstructed reactions using purified RNA
polymerase II plus cell fractions containing partially purified
transcription factors.  Experiments will attempt to identify a
phosphoprotein target for Ckinase in in crude extracts; in
purified fractions that stimulate transcription activity; on isolate
transcription complexes from Ad5infected cells and from in vitro
transcription reactions; and from the chromain of TPAtreated
cells.  Phosphoproteins from labeled transcription complexes will
be characterized by two dimensional polyacrylamide gel
electrophoresis and autoradiography.  The effect of Ckinase on
in vitro transcription of other TPAinducible genes will be tested.

## Key facts

- **NIH application ID:** 3175561
- **Project number:** 5R01CA037761-06
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **SAM.gov UEI:** QMCKV4B31PG2
- **Principal Investigator:** TIMOTHY HOWARD CARTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $151,413
- **Award type:** 5
- **Project period:** 1984-07-01 → 1990-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175561

## Citation

> US National Institutes of Health, RePORTER application 3175561, REGULATION OF TRANSCRIPTION BY A TUMOR PROMOTER (5R01CA037761-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175561. Licensed CC0.

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