Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and 
proteasomal degradation of the p53 tumor suppressor protein. Acetylation of p53 
regulates p53's transcriptional activity and inhibits Mdm2-mediated p53 
ubiquitination and degradation. We now report that Mdm2 is also a target for 
acetylation. Mdm2 is acetylated in vitro by CREB-binding protein (CBP) and to a 
lesser extent by p300, but not by p300/CPB-associated factor. Acetylation occurs 
primarily within the RING finger domain of Mdm2. In vivo acetylation of Mdm2 was 
detected easily with CBP but not p300. Efficient in vivo acetylation required 
the preservation of the RING finger. An Mdm2 mutant (K466/467Q) mimicking 
acetylation is impaired in its ability to promote p53 ubiquitination, as well as 
Mdm2 autoubiquitination. Moreover, K466/467Q is defective in promoting p53 
degradation in living cells. We thus suggest that acetyltransferases may 
modulate cellular p53 activity not only by modifying p53, but also by 
inactivating Mdm2.