Separation of C/EBP alpha-mediated proliferation arrest and differentiation pathways

Cell proliferation and terminal differentiation are mutually exclusive in m ost cell lineages. The b-zip transcription factor CCAAT/enhancer-binding pr otein alpha (C/EBP alpha) induces proliferation arrest and differentiation in many cell types, suggesting that both activities are linked, Here we sho w that C/EBP alpha-mediated proliferation arrest and differentiation pathwa ys can be separated by the E7 oncoprotein of the "high-risk" human papillom a virus 16, The E7 oncoprotein overrides C/EBP alpha-mediated cell cycle wi thdrawal without compromising the transactivation activity of C/EBP alpha o r its ability to participate in differentiation. Uncoupling of both pathway s depends on the casein kinase II site of the oncoprotein but not on its ab ility to neutralize pocket proteins or the cyclin-dependent kinase inhibito r protein p21, Our results suggest a bifurcation of C/EBP alpha-mediated pr oliferation arrest and differentiation pathways.