REPRESSION OF THE C-JUN TRANSACTIVATION FUNCTION BY THE ADENOVIRUS-TYPE-12 E1A 52R PROTEIN CORRELATES WITH THE INHIBITION OF PHOSPHORYLATION OF THE C-JUN ACTIVATION DOMAIN

The early region 1A 52R polypeptide, a protein expressed exclusively b y the in vivo oncogenic adenovirus subtype 12, represses the trans-act ivating function of the cellular transcription factor complex AP-1 con sisting of c-Jun-c-Jun homodimers. In this report we demonstrate that the repression in vivo correlates with a direct physical interaction o f the adenovirus protein with c-Jun in vitro. Interestingly, the 52R p rotein binds to the bZIP domain of c-Jun essential for dimerization an d DNA binding but not to the c-dun activation domain. This interaction does not prevent the promoter binding of c-Jun/AP-1. Moreover, the ph ysical association between c-Jun and the TATA box-binding protein TBP is not disturbed by the 52R polypeptide. In fact, we show evidence tha t down-regulation of c-Jun activity by the adenoviral protein is due t o the inhibition of phosphorylation of the c-Jun trans-activation doma in. In vivo phosphorylation of the c-Jun activation domain is necessar y for the interaction of c-Jun with specific cofactors such as CBP and therefore a prerequisite for the activation of target genes. Due to t hese results we propose a model in which the 52R protein represses the trans-activating function of c-Jun by preventing its phosphorylation through a specific kinase necessary for the activation of the cellular transcription factor.