REGULATION OF MUTANT P53

Aging

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Abstract

One of the most effected genes in the human tumors is p53. About 60% of human cancers contain mutation in p53 gene. Although the regulation of p53 is well studied, very little is known about the regulation of mutant p53. We have shown previously that a human B-lymphoma cell line (RL) harboring mutant p53, which is refractory to the growth inhibitory effects of transforming growth factor-beta(TGF-beta),can be rendered sensitive to TGF-beta by induction of receptors for TGF-beta with low concentrations of phorbol myristate acetate (PMA). We have also shown the growth inhibitory effect of TGF-beta was associated with a down regulation of mutant p53. To know the regulation of mutant p53, we are examining the signal transduction molecules involved in the down regulation of mutant p53 by TGF-beta. We are also examining the effect of PFT-a, a newly discovered inhibitor of p53 signaling, on the mutant p53 and the growth of RL cells.