# UTERINE ESTROGEN-BINDING PROTEINS

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1994 · $220,915

## Abstract

The estrogens are essential hormones for regulating normal development,
growth and reproductive functions.  The estrogens, as well as the
estrogenic antagonists mediate their biological actions by their
interactions with the estrogen receptor.  The estrogen receptor in turn
regulates the transcriptional activity of estrogen responsive genes by
its interactions with specific DNA sequence of these genes referred to as
the estrogen responsive elements (ERE).  The long term goal of this
research program is to elucidate the mechanism of estrogen and estrogenic
antagonist interactions with the estrogen receptor, and to gain insight
into the structure-function relationship of the receptor.  The estrogen
receptor is phosphorylated in an estrogen dependent manner immediately
before or after binding to an ERE and as a consequence the gene's
transcriptional activity is promoted.  A major gap in our knowledge and
the focus of this research program is to describe the mechanism(s) by
which the estrogen dependent phosphorylation of the estrogen receptor
regulates the receptor's transcriptional function.  Our working model is
that as a consequence of phosphorylation of the estrogen receptor the
receptor affinity for its ERE is increased and/or changes the
conformation of the estrogen receptor-ERE complexes in such a way to
promote transcriptional activity.  We will identify which crucial
serine(s) of the estrogen receptor is (are) phosphorylated in an estrogen
dependent manner We intend to characterize and identify the specific
protein kinase responsible for the phosphorylation of the receptor.  The
in vivo transcriptional activity of the crucial serine(s) that is
phosphorylated will be assessed using site-directed mutagenesis of the
specific serine(s).  We will determine whether phosphorylation of the
estrogen receptor influences its interaction with the ERE to antagonists
to promote transcriptional activation. The ability of estrogens and
estrogenic antagonists to phosphorylate the crucial serine(s) will be
determined by [32p] labeling  of the estrogen receptor in MCF-7 cells
followed by receptor purification and SDS-gel electrophoresis.  HPLC
isolation of the [32p]labeled tryptic peptide(s) and gas-phase
microsequencing of the peptide(s) will be used to identify the crucial
serine(s) that is phosphorylated in a hormone dependent manner.  These
studies will provide a test of our model and an important insight into a
key step by which the estrogen receptor regulates gene transcription.

## Key facts

- **NIH application ID:** 2194991
- **Project number:** 5R01HD006707-22
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** Thomas A Gasiewicz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $220,915
- **Award type:** 5
- **Project period:** 1975-08-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194991

## Citation

> US National Institutes of Health, RePORTER application 2194991, UTERINE ESTROGEN-BINDING PROTEINS (5R01HD006707-22). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194991. Licensed CC0.

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