Lysine methylation represses p53 activity in teratocarcinoma cancer cells

Significance Cancer progression typically involves inactivation of the p53 tumor suppressor. In testicular teratocarcinoma, there exist unusually high protein levels of wild-type p53, but strikingly, without normal activation of genes up-regulated by p53, such as cell cycle arrest and DNA repair pathways. This suggests that posttranslational mechanisms, such as protein modification, may repress activity of the high levels of wild-type p53. Our findings demonstrate an important role in teratocarcinoma of previously characterized repressive p53 methylation, which down-regulates normal p53 activation functions. The results suggest the potential for novel approaches to reactivate wild-type p53 in teratocarcinoma via therapeutic inhibition of the methyltransferase enzymes that modify p53, which could be similarly appropriate for treatment of other cancers expressing high levels of wild-type p53.