Repression of the c-Jun trans-Activation Function by the Adenovirus Type 12 E1A 52R Protein Correlates with the Inhibition of Phosphorylation of the c-Jun Activation Domain

• Published in: The Journal of biological chemistry 1995-05, Vol.270 (18), p.10754-10763
• Main Authors: Brockmann, Dieter, Bury, Carsten, Kröner, Gabriele, Kirch, H.-Christoph, Esche, Helmut
• Format: Article
• Language: English
• Subjects: Adenovirus E1A Proteins - metabolism; Adenovirus E1A Proteins - pharmacology; Adenoviruses, Human - genetics; DNA-Binding Proteins - metabolism; Leucine Zippers; Phosphorylation; Protein Binding; Proto-Oncogene Proteins c-jun - antagonists & inhibitors; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Proteins; TATA-Box Binding Protein; Transcription Factors - metabolism; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.18.10754

The early region 1A 52R polypeptide, a protein expressed exclusively by the in vivo oncogenic adenovirus subtype 12, represses the trans-activating function of the cellular transcription factor complex AP-1 consisting of c-Jun-c-Jun homodimers. In this report we demonstrate that the repression in vivo correlates with a direct physical interaction of the adenovirus protein with c-Jun in vitro. Interestingly, the 52R protein binds to the bZIP domain of c-Jun essential for dimerization and DNA binding but not to the c-Jun activation domain. This interaction does not prevent the promoter binding of c-Jun/AP-1. Moreover, the physical association between c-Jun and the TATA box-binding protein TBP is not disturbed by the 52R polypeptide. In fact, we show evidence that down-regulation of c-Jun activity by the adenoviral protein is due to the inhibition of phosphorylation of the c-Jun trans-activation domain. In vivo phosphorylation of the c-Jun activation domain is necessary for the interaction of c-Jun with specific cofactors such as CBP and therefore a prerequisite for the activation of target genes. Due to these 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.