Poly(ADP-ribosyl)ation of p53 in vitro and in vivo modulates binding to its DNA consensus sequence

The tumor-suppressor p53 undergoes extensive poly(ADP-ribosyl)ation early d uring apoptosis in human osteosarcoma cells, and degradation of poly(ADP-ri bose) (PAR) attached to p53 coincides with poly(ADP-ribose)polymerase-1, (P ARP-1) cleavage, and expression of p53 target genes. The mechanism by which poly(ADP-ribosyl)ation may regulate p53 function has now been investigated . Purified wild-type PARP-1 catalyzed the poly(ADP-ribosyl) of full-length p53 in vitro. In gel supershift assays, poly(ADP-ribosyl)ation suppressed p 53 binding to its DNA consensus sequence; however, when p53 remained unmodi fied in the presence of inactive mutant PARP-1, it retained sequence-specif ic DNA binding activity. Poly(ADP-ribosyl)ation of p53 by PARP-1 during ear ly apoptosis in osteosarcoma cells also inhibited p53 interaction with its DNA consensus sequence; thus, poly(ADP-ribosyl)ation may represent a novel means for regulating transcriptional activation by p53 in vivo.