Reisman Lab p53 Tumor Suppressor Home Page
Welcome to our Laboratory
The wild type p53 gene is a tumor suppressor gene which encodes a protein that regulates a cell cycle checkpoint and the induction of programmed cell death (apoptosis) in response to DNA damage, cell stress or the aberrant expression of some oncogenes. Missense mutations in the p53 gene, which inactivate its growth suppressing activities, have been observed in over 60% of all human tumors. In a number of cases elevated transcription of the p53 gene contributes the overall high levels of the mutant protein in tumor cells. Unlike other tumor suppressors where loss of function is sufficient to promote tumorigenesis, greater than 75% of the observed mutations in p53 are missense mutations that, in some cases, may confer some selective advantage to cells expressing them. The ability of many mutant and oncogenic tumor-derived p53 alleles to modulate gene expression may be of prime importance in their transforming and oncogenic activities since missense mutations are very rarely observed in either the amino terminal transactivation domain of the protein or in the nuclear localization signals.
The expression of the p53 gene is under highly regulated control which when perturbed can lead to deregulated expression of the gene and also contribute to tumor progression. Interestingly, transcription of the p53 gene has been found to be induced as cells enter S-phase. We have been working towards defining the factors required for this S-phase expression as well as the biological consequences of expressing the p53 gene in early S-phase. Our recent findings demonstrate that elevated the elevated level of p53 mRNA found in cells during S-phase provides a mechanism whereby cells can respond quickly to DNA damage as cells are in the process of synthesizing DNA. The major goals of our research therefore are to define the role that mutant p53 plays in transformation and to determine the mechanisms responsible for normal p53 expression and those that lead to de-regulated expression of the p53 gene in tumor cells.
Takahashi, P., Polson, A., and Reisman. D. 2010. p53 response to DNA damage during S-phase. Nature Procedings <http://hdl.handle.net/10101/npre.2010.4403.1>
Polson, A., Takahashi, P., and Reisman, D. 2010. Chromatin immunoprecipitation (ChIP) analysis demonstrates coordinated binding of two transcription factors to the promoter of the p53
tumor suppressor gene. Cell Biol. Int. in press
Boggs, K., Henderson, B., and Reisman, D. 2009. The transcription factor RBPk acts to repress p53 expression in a tissue specific fashion. Cell Biol. Int. 33, 318-324.
Boggs, K. and Reisman, D. 2007. The transcription factor C/EBP is essential for cell cycle regulation of the p53 gene. J. Biol. Chem. 282, 7982-7990.
Reisman, D. and Boggs, K. 2007. Transcriptional regulation of the p53 tumor suppressor gene: a potential target for cancer therapies? Recent Patents
on DNA and Gene Sequences 1, 176-185
Thomas, S. and Reisman, D. 2006. Localization of a mutant p53 response element on the Tissue Inhibitor of Metalloproteinase-3 promoter: mutant p53
activities are distinct from wild-type. Cancer Letters, 240, 48-59.
Boggs, K. and Reisman, D. 2006. The induction of p53 transcription prior to DNA synthesis is regulated through a novel regulatory element within the p53
promoter. Oncogene 25, 555-565.
Reisman, D. Wallace, J., and Lu. G. 2004. Loss of heterozygosity and p53 expression in Pterygium. Cancer Letters, 206 77 - 83.
Reisman, D., Balint, E., Loging, W.T., Rotter, V., and Almon, E., 1996 A novel transcript encoded within the 10-kb first intron of the human p53 tumor suppressor gene (D17S2179E) is induced during the differentiation of myeloid leukemia cells Genomics 39, 1648-1653.
Roy, B., Beamon, J., Balint, E. and Reisman. 1994. Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors. Mol. and Cell. Biol. 14, 7805-7815.
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Transformed Mouse Fibroblasts Expressing Mutant p53
Probably two of the most complete sites containing information on p53:
Crystal Structure of p53 bound to DNA
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