Separation of C/EBPalpha-mediated proliferation arrest and differentiation pathways.
Cell proliferation and terminal differentiation are mutually exclusive in most cell lineages. The b-zip transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) induces proliferation arrest and differentiation in many cell types, suggesting that both activities are linked. Here we show that C/EBPalpha-mediated proliferation arrest and differentiation pathways can be separated by the E7 oncoprotein of the "high-risk" human papilloma virus 16. The E7 oncoprotein overrides C/EBPalpha-mediated cell cycle withdrawal without compromising the transactivation activity of C/EBPalpha or its ability to participate in differentiation. Uncoupling of both pathways depends on the casein kinase II site of the oncoprotein but not on its ability to neutralize pocket proteins or the cyclin-dependent kinase inhibitor protein p21. Our results suggest a bifurcation of C/EBPalpha-mediated proliferation arrest and differentiation pathways.
Müller
C
C
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany.
Alunni-Fabbroni
M
M
Kowenz-Leutz
E
E
Mo
X
X
Tommasino
M
M
Leutz
A
A
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D014157:Transcription Factors / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16