Control of p53 turnover is critical to p53 function. E1A binding to p3
00/CBP translates into enhanced p53 stability, implying that these coa
ctivator proteins normally operate in p53 turnover control. In this re
gard, the p300 C/H1 region serves as a specific in vivo binding site f
or both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover
, most of the endogenous MDM2 is bound to p300, and genetic analysis i
mplies that specific interactions of p53 and MDM2 with p300 C/H1 are i
mportant steps in the MDM2-directed turnover of p53. A specific role f
or p300 in endogenous p53 degradation is underscored by the p53-stabil
izing effect of overproducing the p300 C/H1 domain. Taken together, th
e data indicate that specific interactions between p300/CBP C/H1, p53,
and MDM2 are intimately involved in the MDM2-mediated control of p53
abundance.