# THE MOLECULAR BIOLOGY OF SV40 LARGE T ANTIGEN

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1987 · $174,432

## Abstract

SV40 large T antigen is a multifunctional protein involved in the
regulation of viral and cellular gene expression.  Mutants have played an
important role in studies of the molecular biology of SV40 large T
antigen.  Previously, a large set of mutants with deletions at Dde I sites
in the early region was prepared in this laboratory.  Subsequent studies
will focus on the transformation potentials of these mutants and the
biological and biochemical properties of the mutant large T antigens.  One
principle aim is to determine whether mutants alone unable to transform
primary cells can complement one another, or cloned oncogenes, to transform
primary cells.  Specific cellular genes are activated by SV40
transformation--additional studies will be directed at determining whether
the same cellular genes are also activated in mutant-transformed cell
lines.  Studies on the oligomerization behavior of mutant large T antigens,
their subcellular localization, and their affect on transcription for the
SV40 late promoter will also be conducted.

Previously, studies in this laboratory determined that the carboxy-terminal
portion of large T provides a function needed for efficient growth of SV40
in primary cells or CV-1 (and related) lines.  Mutants unable to express
this domain are blocked at a late stage of infection, but grow normally in
BSC-1 and Vero cells.  This domain can be transferred to VP1 and remains
functional, indicating that T antigen contains at least 2 separable
functional domains.  In the coming period, this late function of large T
will be studied in detail.  Answers to the following questions will be
sought:  Is the function involved in determining either the tissue or
species growth range of SV40?  Will mutants unable to express this domain
grow in hybrids between permissive (BSC-1) and non-permissive (CV-1)
cells?  At the molecular level, what defects are exhibited by these
mutants?  Can mutations at sites distant from the original deletion bring
about reversion of the phenotype of these mutants?

Major portions of the SV40 A gene, encoding large T antigen, have not yet
been studied with sophisticated genetic tools.  Therefore, additional
mutants will be prepared with small insertions (using oligonucleotide
linkers) or deletions at Aha III sites in the SV40 early region.  These
sites are clustered in portions of the A gene of interest.  These mutants
will be characterized for their biological and biochemical properties,
including their potential for malignant transformation.

## Key facts

- **NIH application ID:** 3178100
- **Project number:** 5R01CA039259-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** CHARLES N. COLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $174,432
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178100

## Citation

> US National Institutes of Health, RePORTER application 3178100, THE MOLECULAR BIOLOGY OF SV40 LARGE T ANTIGEN (5R01CA039259-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178100. Licensed CC0.

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