# CONTROL OF RRNA SYNTHESIS BY CARCINOGENS AND HORMONES

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 1990 · $246,826

## Abstract

The long term objectives of this research are to elucidate the mechanisms
for the regulation of ribosomal RNA synthesis. Recently, we have purified a
37bp enhancer-binding protein (E1BF) which consists of two polypeptides,
and have also partially characterized a 43bp enhancer-binding protein
(E2BF). Both E1BF and E2BF bind to the core promoter as well, and E1BF
enhances Pol I-directed transcription from the core promoter as much as
10-fold even under nonoptimal conditions. The specific aims of the current
proposal are (a)to determine whether the two E1BF polypeptides are
structurally related. (This will be done by peptide mapping following CNBr
or V8 protease cleavage), (b) to investigate whether one of the
polypeptides binds to the enhancer and the other to core promoter by the
electrophoretic mobility shift and DNase I protection analyses, (c) to
study the function of these polypeptides (d) to determine the core or
consensus element(s) in the enhancer by a combination of deletion and
linker scanning mutagenesis. We will explore (1) the species-specific
action, (2) effect on pre-initiation complex formation, initiation and
elongation reactions (3) probable existence of two domains, one binding to
DNA and the other exhibiting a "transcriptionally active" region and (4)
binding to other enhancer elements in the spacer. We will also attempt to
distinguish "scanning model" from a "looping model" to explain the action
of the enhancer. We will then clone the gene for E1BF, express it in
bacteria, study the function of the bacterially produced protein, determine
the cDNA and peptide sequences, examine relationship, if any, of the gene
and its product to those of other known genes and polypeptides and study
the expression of this gene under different conditions such as
glucocorticoid-induced stimulation in liver, serum-dependent growth, in
hepatoma vs resting liver, all of which lead to up regulation of rRNA
synthesis, and cycloheximide treatment and serum deprivation which result
in down regulation of rRNA synthesis. Phosphorylation and dephosphorylation
of E1BF and Pol I under the above conditions will also be examined. The
effect of phosphorylation on the binding E1BF to the core promoter and
enhancer, and on the stability of the initiation complex will also be
studied. Finally, these studies win be extended to E2BF, the 43bp
motif-binding factor. It is anticipated that these studies will reveal the
basic molecular mechanism (s) for the regulation of ribosomal RNA
synthesis, a key cellular event, in growth, tumorigenesis and following
hormone treatment.

## Key facts

- **NIH application ID:** 3170003
- **Project number:** 2R01CA031894-09
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **SAM.gov UEI:** V913TCT2SFZ9
- **Principal Investigator:** SAMSON T JACOB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $246,826
- **Award type:** 2
- **Project period:** 1989-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170003

## Citation

> US National Institutes of Health, RePORTER application 3170003, CONTROL OF RRNA SYNTHESIS BY CARCINOGENS AND HORMONES (2R01CA031894-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170003. Licensed CC0.

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