# ADENOVIRUS LP LOCUS:  ROLE IN ONCOGENIC TRANSFORMATION

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 1993 · $205,244

## Abstract

Adenovirus E1b region-coded 19K tumor antigen plays an important role in
cell transformation in cooperation with  the E1a proteins. We propose to
investigate the role of 19K in adenovirus-mediated transformation using
genetic and biochemical approaches. It appears that E1a-mediated
transformation may be negatively regulated by other early viral genes. We
will investigate the effect of the 19K gene relieving the transformation
inhibitory effect of other early genes by DNA transfection and by using
viral double mutants.  Physical association of 19K with other early
proteins will be studied by coimmunoprecipitation analysis of proteins
cross-linked in living cells. Other early genes that interact with 19K
protein will also be investigated using revertants of a 19K mutant, cyt6.
The site of reversion will be mapped by marker rescue and by DNA sequence
analysis. One of our major goals would be to identify cellular factors that
physically interact with 19K during transformation. These proteins will be
identified by coimmunoprecipitation analysis of proteins cross-linked in
living cells over-express the 19K protein. The identity of the cellular
proteins will be determinied by partial sequence determination of the genes
coding for these proteins.  To probe the structure and function of 19K,
mutants with one or two amino acid substitutions or deletions will be
constructed in the regions which appear to be functionally important.  We
have noted that a region of the 19K protein is homologous to a region of
polyoma middle T (mT) antigen which is important for trans- formation. We
will study the functional similarity between this 19K protein region and
the corresponding mT protein region by domain substitution. We have
observed that 19K plays a role in calcium mobilization.  We will determine
whether 19K plays a role in signal transduction at the level of generation
of second messengers by studying the turnover of phosphoinositotides. As
19K appears to alter the architecture of the endoplasmic reticulum, we will
also investigate whether 19K plays a role in calcium release from the
endoplasmic reticulum by using isolated ER membrane vesicles in the
presence of inositol tris- phosohate (InsP3). The 19K protein contains an
amphipathic acidic domain similar to the calcium regulating domain of
epidermal growth factor receptor (EGFR) and related receptors. To determine
whether the acidic domain of 19K is functionally similar to this EGFR
domain, we will construct a chimeric EGFR in which the acidic domain is
replaced with the corresponding domain of 19K. The role of the chimeric
receptor in calcium mobilization and ligand-dependent internalization will
be determined. The proposed studies should facilitate understanding of the
biochemical mechanism of 19K-mediated transformation.

## Key facts

- **NIH application ID:** 3171427
- **Project number:** 5R01CA033616-14
- **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:** 1993
- **Award amount:** $205,244
- **Award type:** 5
- **Project period:** 1979-07-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171427

## Citation

> US National Institutes of Health, RePORTER application 3171427, ADENOVIRUS LP LOCUS:  ROLE IN ONCOGENIC TRANSFORMATION (5R01CA033616-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171427. Licensed CC0.

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