The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is 
regulated by posttranslational modifications, such as phosphorylation or 
ubiquitination. In addition, covalent attachment of the ubiquitin-like modifier 
SUMO appears to modulate their transcriptional activity. Sumoylation proceeds 
via an enzymatic pathway that is mechanistically analogous to ubiquitination, 
but requires a different E1-activating enzyme and Ubc9, a SUMO-specific 
E2-conjugating enzyme. Here, we show that two members of the PIAS family, PIAS1 
and PIASxbeta, act as specific E3-like ligases that promote sumoylation of p53 
and c-Jun in vitro and in vivo. The PIAS proteins physically interact with both 
p53 and c-Jun. In addition, they bind to Ubc9, suggesting that they recruit the 
E2 enzyme to their respective substrate. The SUMO ligase activity requires the 
conserved zinc-finger domain, which is distantly related to the essential 
RING-finger motif, found in a subset of ubiquitin ligases. Furthermore, similar 
to RING-type ubiquitin ligases, PIASxbeta can catalyze its own modification. 
Hence, these data further extend the analogy between the ubiquitin and SUMO 
pathway. Strikingly, PIAS proteins strongly repress the transcriptional activity 
of p53, suggesting that the PIAS-SUMO pathway plays a crucial role in the 
regulation of p53 and presumably other transcription factors.