Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver.
The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA synthesis, in the number of mitosis and of phosphorylated histone H3-positive cells. The post-PH proliferation peak is delayed by 10 hr, indicating an altered hepatocyte cell cycle. Expression of cyclins A, B, D1, E, and cdc2, of c-fos and tyrosine aminotransferase is deregulated. CREM mutation results in delayed S-phase entry, impairing the synchronization of proliferation.
Servillo
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université Louis Pasteur (CNRS-INSERM-ULP), 67404 Illkirch, Strasbourg,
Della Fazia
M A
MA
Sassone-Corsi
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P
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D000242:Cyclic AMP; D051786:Cyclic AMP Response Element Modulator; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration; D051379:Mice; D008817:Mice, Mutant Strains; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D016213:Cyclins; D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D016203:CDC2 Protein Kinase