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.
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.
Brockmann
D
D
Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Federal Republic of Germany.
Bury
C
C
Kröner
G
G
Kirch
H C
HC
Esche
H
H
D017500:Adenovirus E1A Proteins / Q000378:metabolism / Q000494:pharmacology*; D000260:Adenoviruses, Human / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016350:Leucine Zippers; D010766:Phosphorylation; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors