C/EBP beta isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Tom LueddeC Trautwein

Abstract

The CCAAT enhancer-binding protein (C/EBP) beta gene can produce several N-terminally truncated isoforms. Liver-enriched activator protein (LAP) is a transcriptional activator in many systems, whereas liver-enriched inhibitory protein (LIP) is regarded as a functional LAP antagonist. In this study, we examined the impact of these two proteins on cell cycle progression in the regenerating liver. Adenoviral overexpression of LAP, in addition to its role as a transactivator of liver-specific genes, led to a delayed S-phase entry of hepatocytes after partial hepatectomy (PH) in vivo. This delay was accompanied by decreased expression of cyclin A and E as well as proliferating cell nuclear antigen and decreased cyclin-dependent kinase 2 activity at the G1/S boundary. This observation is not explained by increased p21(CIP1/Waf1) expression or lack of phosphorylation of external LAP, but LAP overexpression triggered a decreased C/EBP-alpha/C/EBP-alpha-30 ratio and a reduced basal c-jun level in the liver. In contrast, adenoviral overexpression of LIP resulted in a stronger and earlier induction of cyclin A and E after PH, but did not change the timing and extent of cyclin-dependent kinase 2 activity or the amount of hepatocytes that e...Continue Reading

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Citations

Jun 1, 2005·Journal of Hepatology·Bin WangKatherine Parker Ponder
Feb 25, 2010·The Journal of Biological Chemistry·François MarchildonNadine L Wiper-Bergeron
May 26, 2010·The Journal of Biological Chemistry·Daniel OrellanaNikolai A Timchenko
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