THE DNA-BINDING AND TRANSCRIPTION-ACTIVATION ABILITIES OF P53 ARE NECESSARY BUT NOT SUFFICIENT FOR ITS ANTIPROLIFERATION FUNCTION

Normal p53 protein suppresses cell proliferation and ras oncogene-indu ced cell transformation. Missense mutations in the middle conserved co nformational domain of p53 decrease its antiproliferation function. In this work, we studied the requirement of the NH2- and COOH-terminal r egions of p53 in its antiproliferation function using two independent assays, growth of chronic myelogenous leukemia K562 cells on methylcel lulose semisolid medium and ras oncogene-induced focus formation of ra t fibroblast cells (Rat-1). We found that deletion of 80 or 159 amino acids from the NH2-terminus and deletion of 67 amino acids from the CO OH-terminus of p53 drastically reduced the antiproliferation function of p53. However, the COOH-terminal deletion mutant is capable of bindi ng to a p53 DNA-binding element, p53CON (GGACATGCCCGCGCATGTCC), and of activating p53CON-mediated transcription. These results suggest that p53' abilities to bind p53CON and activate transcription are not suffi cient for its antiproliferation function and that p53CON-regulated gen es may not be growth suppressive.