Phosphorylation at multiple sites within the N-terminus of p53 promotes its dissociation from hdm2/mdm2 and sti-mulates its transcriptional regulatory potential. The large phosphoinositide 3-kinase-like kinases ataxia telangiectasia mutated gene product and the ataxia telangectasia and RAD-3-related kinase promote phosphorylation of human p53at Ser15andSer20, andare required for theactivationof p53 following DNA damage. DNA-dependent protein kin-ase (DNA-PK) is another large phosphoinositide 3-kinase-like kinase with the potential to phosphorylate p53 at Ser15, and has been proposed to enhance phosphorylation of these sites in vivo
