# NUCLEAR TARGETING OF PROTEIN

> **NIH NIH R01** · WORCESTER FOUNDATION FOR BIOMEDICAL RES · 1992 · $292,561

## Abstract

The protein encoded by the adenovirus E1A gene has several
biological activities including the stimulation of transcription
of some genes, the repression of transcription of other genes, and
cell immortalization and transformation.  This proposal will
examine two aspects of the E1A.  First, it is now generally
accepted that nuclear proteins, of which E1A is an example, contain
within their primary sequences discrete regions that target them
to the nucleus.  E1A is unusual in that it contains two nuclear
targeting domains that are differentially used during development.
The fine structure of these domains will be assessed as well as the
exact time during development when each is used.  The experiments
will be performed in the convenient model system, oocytes and
embryos of the frog Xenopus laevis.  E1A mutants will be
constructed such that certain amino acid residues are deleted from
the protein.  In addition, chimeric proteins will be constructed
that fuse certain regions of E1A to B-galactosidase.  All
constructions will be performed at the DNA level, and the resulting
mutant proteins will be expressed either in vitro or in vivo.  The
second aspect of E1A to be examined is its rate of turnover.  E1A
normally has a very short half-life within cells.  This proposal
will extend preliminary observations that E1A turnover is related
to mRNA translation and that the amino terminal region of E1A is
indispensible for instability.  This proposal will assess the
connection between E1A translation and instability.  These
experiments will also make use of deletion and chimeric E1A mutants
similar to those described above.  Protein turnover will be assayed
in injected Xenopus oocytes and transfected somatic cells.

E1A greatly influences growth control of cells.  Therefore, a
deciphering of the mechanism by which it enters the nucleus, where
it exerts its effects, and the length of time it remains active
within cells are of crucial importance for our understanding of
cancer.

## Key facts

- **NIH application ID:** 3179831
- **Project number:** 5R01CA040189-08
- **Recipient organization:** WORCESTER FOUNDATION FOR BIOMEDICAL RES
- **Principal Investigator:** Joel D Richter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $292,561
- **Award type:** 5
- **Project period:** 1985-07-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179831

## Citation

> US National Institutes of Health, RePORTER application 3179831, NUCLEAR TARGETING OF PROTEIN (5R01CA040189-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179831. Licensed CC0.

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