# NUCLEAR TARGETING OF PROTEIN

> **NIH NIH R01** · WORCESTER FOUNDATION FOR BIOMEDICAL RES · 1987 · $99,736

## Abstract

This proposal intends to examine the mechanism by which cell-transforming
proteins come to reside in the nucleus.  The adenovirus E1A gene product is
required for the transcription of other adenovirus genes and is involved in
cell transformation and immortalization.  This protein acts at the level of
transcription and has been shown to be concentrated in the nucleus of
cells.  We have used the microinjected Xenopus laevis oocyte to examine
transcriptional activity and nuclear targeting of this protein.  When
overproduced in bacteria to yield a bona fide (nonfusion) protein, E1A
stimulates the transcription of an adenovirus gene in injected oocytes.
When examined for its ability to enter oocyte nuclei following cytoplasmic
injection, however, we show that the protein undergoes a modification such
that its apparent molecular weight increases by about 2,000 daltons.  Only
this modified form of the protein is found in nuclei.  A second
transforming nuclear protein, that encoded by the human c-myc gene, also
undergoes a similar modification in the cytoplasm before it can enter the
nucleus.  The specific aims of this proposal are to determine the nature of
the modification, the amino acid residue(s) it modifies, and its
relationship to nuclear targeting and possible transcriptional regulation.
The modification will be determined by oocyte microinjection of small E1A
peptides, followed by HPLC and amino acid sequencing.  Further studies
include the construction of fusion proteins between E1A and myc and other
nonnuclear proteins via recombinant DNA technology.  The ability of the
fusion proteins to be modified and enter nuclei will be assessed.  The
long-term goals of this project are to determine the signal on proteins
which target them to the nucleus and to investigate determinants on
proteins which might be responsible for transcriptional regulation and
transformation.  Thus, these studies are of basic importance in cellular
and molecular as well as developmental biology.

The gene products which are under investigation have been implicated in the
two-step model for cancer.  Thus, this proposed project has a direct
bearing on our ultimate understanding of cancer.  (K)

## Key facts

- **NIH application ID:** 3179827
- **Project number:** 5R01CA040189-03
- **Recipient organization:** WORCESTER FOUNDATION FOR BIOMEDICAL RES
- **Principal Investigator:** Joel D Richter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $99,736
- **Award type:** 5
- **Project period:** 1985-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179827

## Citation

> US National Institutes of Health, RePORTER application 3179827, NUCLEAR TARGETING OF PROTEIN (5R01CA040189-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179827. Licensed CC0.

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