University of South Carolina

Reisman Lab p53 Tumor Suppressor Home Page

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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.


SELECTED PUBLICATIONS:

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.

Durland-Busbice, S. and Reisman, D. 2002. The lack of p53 expression in human myeloid leukemias is not due to mutations in transcriptional regulatory regions of the gene. Leukemia, 16 2165 - 2167.

Reisman, D., Eaton, E., McMillin, D., Doudican, N. and Boggs, K. 2001. Cloning and characterization of murine upstream sequences reveals additional positive regulatory elements. Gene, 274, 129-137.

Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, Marks J, and Sukumar S. 2000 Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature, 405, 974-978.

Loging, W.T. and Reisman, D. 1999 Inhibition of the putative tumor suppressor gene TIMP-3 by tumor-derived p53 mutants and wild type p53. Oncogene, 18, 7608-7613.

Loging, W.T. and Reisman, D. 1999 Elevated Expression of Ribsomal Protein Genes RPP-1, L37, and S2 in the Presence of Mutant p53. Cancer Epidemiology, Biomarkers, and Prevention 8,1011-6.

Reisman, D. and Loging, W.T. 1998 Transcriptional Regulation of the p53 Tumor Suppressor Gene Seminars in Cancer Biology 8, 317-324.

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. and Reisman, D. 1996 Positive and negative regulatory elements contribute to expression of the p53 tumor suppressor gene Oncogene 13, 2359-2366.

Balint, E. and Reisman, D. 1996 Increased rate of transcription contributes to elevated expression of the mutant p53 gene in Burkitt's lymphoma cells. Cancer Research 56, 1648-1653.

Uttenbogaard, M.N., Giebler, H.A., Reisman, D., and Nyborg, J.K. 1995. Transcriptional repression of p53 by the human T-cell leukemia virus type I tax protein. J. Biol. Chem. 270, 28503-28506.

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.

Please E-Mail your questions and comments to:

reisman@biol.sc.edu

Transformed Mouse Fibroblasts Expressing Mutant p53

Probably two of the most complete sites containing information on p53:

·         The Thierry Soussi p53 Site at the Institut Curie

·         The p53 Mutation Database [contains data on over 20,000 tumor samples]


Crystal Structure of p53 bound to DNA

Some other relevant sites:

·         Center for Colon Cancer Research (CCCR)

·         The American Cancer Society

·         The National Cancer Institute

·         The National Institutes of Health

·         Department of Biology

·         College of Arts and Sciences

·         University of South Carolina


People in the Lab:


People in the Lab:


This page was started in October 1995
making it one of the first p53 Websites


http://counter.digits.com/wc/-d/4/p53counter

 

In accordance with USC Policy ACAF 7.04 the following information is included:
Department:
Biological Sciences; Maintainer: Clint Cook BMA cookc@mail.biol.sc.edu
Copyright 1999 by the Board of Trustees of the
University of South Carolina.
This is <URL:http://www.biol.sc.edu/~reisman/index.html> last modified April 2010