ADENOVIRUS E1A NEGATIVELY AND POSITIVELY MODULATES TRANSCRIPTION OF AP-1 DEPENDENT GENES BY DIMER-SPECIFIC REGULATION OF THE DNA-BINDING AND TRANSACTIVATION ACTIVITIES OF JUN

Adenovirus E1A proteins inhibit expression of the collagenase gene but activate expression of the c-jun gene. Both effects are mediated by T PA-responsive elements (TREs), the binding sites for members of the AP -1 transcription factor family. By a process that is independent of th e retinoblastoma gene product, E1A distinguishes between different AP- 1 factors: in vivo binding of Jun/Jun homodimers and Jun/Fos heterodim ers to the collagenase TRE is totally blocked by E1A while, in contras t, there is no inhibition of Jun/ATF-2 binding to the TRE sequences in the c-jun promoter. Altered phosphorylation of the DNA binding domain of cJun is not involved in the inhibition of cJun/cJun and cJun/cFos binding. E1A does, however, cause hyperphosphorylation of the transact ivation domain of cjun, which is likely to be responsible for the enha nced c-jun transcription by E1A mediated through cJun/ATF-2 heterodime rs.