THE CR-1 AND CR3 DOMAINS OF THE ADENOVIRUS TYPE-5 E1A PROTEINS CAN INDEPENDENTLY MEDIATE ACTIVATION OF ATF-2

The adenovirus 12S E1A protein can stimulate the activity of the c-jun promoter through a conserved region 1 (CR1)-dependent mechanism. The effect is mediated by two AP-1/ATF-like elements, jun1 and jun2, that preferentially bind c-Jun-ATF-2 heterodimers. In this study, we show t hat the ATF-2 component of the c-Jun-ATF-2 heterodimer is the primary target for 12S EIA: 12S EIA can enhance the transactivating activity o f the N terminus of ATF-2 when fused to a heterologous DNA-binding dom ain, whereas the transactivating activity of the c-Jun N terminus is n ot significantly affected. Activation of the ATF-2 N terminus by 12S E 1A is dependent on CR1. In the context of the 13S E1A protein, CR1 and CR3 can both contribute to activation of ATF-2, and their relative co ntributions are dependent on the cell type. In contrast to activation of ATF-2 by stress-inducing agents, CR1-dependent activation of ATF-2 was found not to depend strictly on the presence of threonines 69 and 71 in the N terminus of ATF-2, which are targets for phosphorylation b y stress-activated protein kinases (SAPKs). In agreement with this obs ervation, we did not observe phosphorylation of threonines 69 and 71 o r constitutively enhanced SAPK activity in E1A- plus E1B-transformed c ell lines. These data suggest that CR1 dependent activation of ATF-2 b y 12S E1A does not require phosphorylation of threonines 69 and 71 by SAPK.