Aryl hydrocarbon receptor is required for p300-mediated induction of DNA synthesis by adenovirus E1A

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription fac tor that mediates the biological responses to environmental contaminants su ch as 2,3,7,8- tetrachlorodibenzo-p-dioxin. Embryonic fibroblast (EF) isola ted from AHR-null mice exhibited slow cell growth compared with wild-type E F. Reintroduction of AHR into AHR-null EF increased cell growth, suggesting that AHR is involved in cell cycle control. The role of the AHR in cell cy cle control was examined using the adenovirus oncoprotein E1A. EF, derived from wild-type and AHR-null mice, were transfected with two mutant E1A expr ession plasmids that inactivate either p300/CBP or retinoblastoma protein ( pRb). Although DNA synthesis of wild-type EF was induced by both E1A mutant s, DNA synthesis in the AHR-null EF was induced only by the mutant that bin ds pRb, not by the mutant to p300/CBP. These data show that both pRb and p3 00/CBP were the target of E1A-induced DNA synthesis in wild-type EF. In AHR -null mice, however, only pRb was the target of E1A-induced DNA synthesis a nd p300/CBP cannot be inactivated by E1A in the absence of AHR. Immunopreci pitation revealed that AHR directly bound to p300, thus suggesting the intr iguing possibility that AHR is involved in control of the cell cycle via in teraction with p300.