THE HUMAN TUMOR-SUPPRESSOR GENE P53 IS ALTERNATIVELY SPLICED IN NORMAL-CELLS

Alternative splicing affecting the p53 carboxy-terminus has previously been described in mouse but not in normal human cells. We report here the detection in normal human lymphocytes of an alternatively spliced form of human p53 mRNA containing an additional 133 bp exon derived f rom intron 9. This splice variant encodes a truncated protein of 341 a mino-acids including 10 new amino-acids derived from the novel exon. T he truncated protein, which lacks part of the p53 tetramerization doma in, fails to bind DNA in vitro and has transcriptional defect in vivo in both yeast and mammalian cells. Quantitative RT-PCR experiments sug gests that the alternatively spliced form is only present in significa nt amounts in quiescent cells. Considering the numerous functions ascr ibed to the carboxy-terminus of the p53 protein, this splice variant m ay have important implications for the biological role of p53 in norma l cells.