Servillo G, Della Fazia M A, Sassone-Corsi P
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,
Genes Dev. 1998 Dec 1;12(23):3639-43. doi: 10.1101/gad.12.23.3639.
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.
在部分肝切除（PH）后，肝脏会再生，因为终末分化的肝细胞会经历一个巨大的增殖过程。在肝脏再生过程中，CREM基因的表达被强烈诱导。我们发现，在PH后，CREM基因敲除小鼠的细胞增殖显著降低。DNA合成减少，有丝分裂数量以及磷酸化组蛋白H3阳性细胞数量减少。PH后的增殖峰值延迟了10小时，表明肝细胞细胞周期发生了改变。细胞周期蛋白A、B、D1、E和cdc2、c-fos以及酪氨酸转氨酶的表达失调。CREM突变导致S期进入延迟，损害了增殖的同步性。
