Differential interactions of the CREB/ATF family of transcription factors with p300 and adenovirus E1A.

The adenovirus E1A-associated protein p300 is a transcriptional cofactor that interacts with YY1 and mediates the relief of YY1 transcriptional repression by E1A. These observations raise the possibility that p300 may function as a bridging factor between E1A and cellular transcription factors. Here we show that p300, but not a mutant defective for binding to E1A, activated cAMP-responsive element-binding protein/activating transcription factor (CREB/ATF) binding site-mediated transcription in the presence of E1A. Among proteins that can recognize the CREB/ATF site, CREB appeared to be modulated by E1A in a p300 binding-dependent manner. This effect of E1A was correlated with a specific physical interaction between CREB and p300. These results suggest that p300 plays a crucial role in mediating the functional interplay between E1A and certain members of the CREB/ATF family. Two separate domains within p300 were identified that are capable of activating transcription. One of the domains interacted with the basal factor TFIIB, suggesting that p300 may function as a coactivator by making contacts with both sequence-specific transcription factors and the basal transcriptional machinery. This pivotal role of p300 may make it a prime target for viral proteins such as E1A in programming the cellular transcription machinery.