Adenovirus E4orf6 oncoprotein modulates the function of the p53-related protein, p73

Recently, several proteins have been identified that are related in their s equence to the p53 tumor-suppressor protein. One of these proteins, which i s termed p73, exhibits sequence homology to the p53 transcriptional activat ion, DNA binding, and oligomerization domains. The adenovirus E1B 55-kDa pr otein, the adenovirus E4orf6 protein, and SV40 T antigen each can bind to p 53 and inhibit p53 function. Here we demonstrate that the adenovirus E4orf6 protein, but not the E1B 55-kDa protein or T antigen, interacts with p73. The E40rf6 protein inhibits p73-mediated transcriptional activation and cel l killing in a manner similar to its effect on p53. Thus, only a subset of viral oncoproteins that antagonize p53 function also interacts with the rel ated p73 protein.