Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1

The growth-suppressive properties of p53 are trolled by posttranslational m odifications and by regulation of its turnover rate. Here we show that p53 can be modified ill vitro and ill vivo by conjugation to the small ubiquiti n-like protein SUMO-1. A lysine residue at amino acid position 386 of p53 i s required for this previously undescribed modification, strongly suggestin g that this lysine residue serves as the major attachment site for SUMO-1, Unlike ubiquitin, attachment of SUMO-1 does not appear to target proteins f or rapid degradation but rather, has been proposed to change the ability of the modified protein to interact with other cellular proteins. Accordingly , we provide evidence that conjugation of SUMO-1 to wild-type p53 results i n an increased transactivation ability of p53. We suggest that posttranslat ional modification of p53 by SUMO-1 conjugation provides a novel mechanism to regulate p53 activity.