# ADENOVIRUS LP LOCUS:  ROLE IN ONCOGENIC TRANSFORMATION

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 1988 · $129,458

## Abstract

Adenovirus 1p+ locus codes for a 19kd (175R) T antigen which plays an
important role in cell transformation and tumorigenesis.  We propose to
carry out an in depth investigation to elucidate the structure and function
of this protein.  A library of Ad2 mutants with single amino acid
substitutions as well as second-site revertants of selected viral mutants
will be constructed by local mutagenesis.  These mutants and revertants
will be used to correlate the structure and functional domains of this
protein with its involvement in cell transformation, tumorigenicity, and
transformation associated characteristics.  The transformation and
tumorigenicity of the mutant DNAs will be studied using replication
defective murine retrovirus vectors or by use of transformed cells in
newborn hamsters.  Ad2 mutants with possible compensating mutations mapping
outside the 175R coding region will also be isolated in order to identify
other viral genes that may interact with the 175R protein.  Temperature
sensitive mutants will be used to find out whether the 175R protein is
involved in the initiation and/or maintenance of cell transformation.
Mutants with specific alterations in the hydrophobic domains which are
possibly involved in membrane association will be constructed in order to
elucidate the structural requirements for membrane association and the
relationship between membrane association and function.  Genetic evidence
indicates that the Ad12 163R protein may control tumorigenicity.  We will
investigate whether the Ad12 protein could contribute to differential
tumorigenicity.  We will investigate whether the Ad12 protein could
contribute to differential tumorigenicity (i.e. the highly oncogenic nature
of Ad12) using DNA constructs expressing Ad2 Ela region and Ad12 163R
region employing murine retrovirus vectors.  It appears that the 175R
protein is required for CA++ mobilization in transformed cells.  We will
investigate whether the 175R protein could mediate the release of Ca++ from
intracellular stores (endoplasmic reticulum) by an inositol triphosphate
sensitive mechanism.  Since 175R T antigen is also localized on the nuclear
envelope, we will investigate whether this protein could play a role in the
nucleocytoplasmic transport of RNA via enhanced nucleoside triphophatase
activity.

## Key facts

- **NIH application ID:** 3171423
- **Project number:** 5R01CA033616-09
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **SAM.gov UEI:** JNBLLTBTLLD8
- **Principal Investigator:** GOVINDASWAMY CHINNADURAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $129,458
- **Award type:** 5
- **Project period:** 1979-07-01 → 1990-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171423

## Citation

> US National Institutes of Health, RePORTER application 3171423, ADENOVIRUS LP LOCUS:  ROLE IN ONCOGENIC TRANSFORMATION (5R01CA033616-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171423. Licensed CC0.

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