wt p53 dependent expression of a membrane-associated isoform of adenylate kinase

Six novel p53-inducible transcripts were recently cloned from Val5, a murin e cell line stably expressing a temperature-sensitive p53 allele. One of th e isolated clones represented a novel isoform of cytosolic adenylate kinase (AK1), a highly conserved monomeric enzyme involved in cellular homeostasi s of adenine nucleotides. The corresponding protein, which we named AK1 bet a, was specifically induced upon activation of wt p53 in Val5 cells. The AK 1 beta protein differs from cytoplasmic AK1 by having 18 extra amino acids at the N-terminus. The extra residues in AK1 beta provide a consensus signa l for N-terminal myristoylation; as expected, AK1 beta was shown to localiz e to the plasma membrane. The human AK1 gene contains several consensus p53 binding sites and we report that p53-dependent induction of the alternativ e AK1 beta transcript also occurs in human cells. By using antisense ablati on experiments in Val5 fibroblasts we show that AK1 beta plays a relevant r ole in the establishment of reversible cell-cycle arrest as induced by p53 in these cells. These findings suggest that within a p53-dependent genetic program, a specific isoform of adenylate kinase has a previously undescribe d growth regulatory function, which might not necessarily require its best characterized biochemical activity.