# NUCLEAR TARGETING OF PROTEIN

> **NIH NIH R01** · WORCESTER FOUNDATION FOR BIOMEDICAL RES · 1993 · $360,451

## Abstract

The product of the adenovirus ElA gene is a nuclear oncoprotein that has
several biological properties including transcriptional stimulation,
transcriptional repression, and cell transformation and immortalization.
This proposal examines two aspects of ElA, the first of which is the
mechanism of nuclear import.  ElA has two discrete regions that are
responsible for nuclear localization, one that directs nuclear import in
all cells and a second that directs nuclear import in oocytes and
pre-neurula embryonic cells, but not post-neurula cells or adult somatic
cells.  The fine structure of the second region, termed the
developmentally regulated nuclear localization signal (drNLS) has been
precisely defined and shown to be quite different from other NLSs in that
it is devoid of basic residues and is hydrophobic.  An hypothesis to
explain the function of the drNLS is that it interacts with a unique
developmentally regulated cytoplasmic carrier protein.  By a variety of
biochemical methods, the carrier protein will be isolated, cloned, and
tested for importance during development.

Transcriptional stimulation by ElA requires the coordinate activity of
several cellular proteins that bind discrete promoter regions.  One of
these factors, activating transcription factor (ATF), has been partially
cloned from Xenopus.  Developmental profiles of ATF RNA and protein show
these molecules to be very low in oocytes and blastulae, increase
dramatically in gastrulae, and drop precipitously thereafter.  These data
suggest that ATF has an important function during gastrulation.  This
will be explored further by first analyzing ATF spatial expression during
Xenopus development.  To determine whether ATF is necessary for normal
development, a surrogate genetic approach will be employed.  A
full-length ATF cDNA clone will be isolated, sequenced, and used to
misexpress and overexpress wild type and mutant proteins in embryos.  An
analysis of the resulting phenotype will indicate the developmental
process with which ATF is involved.

ElA is a well-known modulator of cell growth control.  An analysis of the
mechanisms by which ElA comes to reside in the nucleus, its site of
action, and an examination of the cellular factors that are influenced by
the protein enhances our understanding of cancer.

## Key facts

- **NIH application ID:** 3179823
- **Project number:** 2R01CA040189-09
- **Recipient organization:** WORCESTER FOUNDATION FOR BIOMEDICAL RES
- **Principal Investigator:** Joel D Richter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $360,451
- **Award type:** 2
- **Project period:** 1985-07-01 → 1998-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179823

## Citation

> US National Institutes of Health, RePORTER application 3179823, NUCLEAR TARGETING OF PROTEIN (2R01CA040189-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179823. Licensed CC0.

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