The Cell Cycle pp 311-317 | Cite as

The Two Amino Terminal Transforming Functions of the SV40 Large T-Antigen are Required to Overcome P53 Mediated Growth Arrest

  • Robin S. Quartin
  • Arnold J. Levine
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


About 60% of cancers from humans contain mutations at the p53 locus1,2. Most commonly, there is a missense mutation in one of the p53 alleles and a loss of the second allele resulting in a reduction to homozygosity of the mutant gene3. Thus p53 behaves like a tumor suppressor gene4 where a loss of function (recessive to wild-type) enhances the probability of cancerous growth. Returning the wild-type p53 gene into cells that are being transformed by an oncogene5 or are already transformed6 blocks the transformation process and, when p53 is expressed at high levels, inhibits cell division of transformed cells. Cells transformed with a temperature sensitive p53 mutant replicate at 37–39°C, where the p53 protein is in a mutant conformation, but fail to grow at 32°C, where the p53 protein is acting as a wild type tumor suppressor1–8. The wild-type p53 protein blocks progression through the cell cycle in G1 7,8. Thus, the wild-type protein can, under certain circumstances9, regulate progression of cells through the cell cycle while mutant p53 proteins fail to do this. The wild-type p53 protein, but not the mutant protein, can act as a transcription factor10–12 and so it is tempting to speculate that p53-mediated transcription of a set of genes can block progression through the cell cycle in the G1 phase of the cycle.


Simian Virus Large Tumor Antigen Primary Mouse Embryo Fibroblast Mutant Conformation Regulate Cell Cycle Events15 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Robin S. Quartin
    • 1
  • Arnold J. Levine
    • 1
  1. 1.Department of Molecular BiologyPrinceton UniversityPrincetonUSA

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