The nuclear phosphoprotein p53 is frequently inactivated in human cancer. Although it was previously classified as an oncoprotein, p53 has emerged as a tumor suppressor controlling cell cycle progression by regulating gene transcription. A major biochemical property of wild-type p53 is its ability to bind DNA in a sequence-specific manner. The human c-H-ras gene contains within its first intron sequences that partially match the p53 consensus binding site. We determined that these sequences represent a bona fide p53 element, since in vitro translated wild-type p53 recognized them with high affinity. Furthermore, wild-type p53 activated transcription from a reporter plasmid containing the c-H-ras element as an enhancer. These findings suggest that p53 regulates cellular growth by coordinate transcription of genes that suppress and promote cellular proliferation.

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