G. Servillo et al., Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver, GENE DEV, 12(23), 1998, pp. 3639-3643
The liver regenerates upon partial hepatectomy (PH) as terminally different
iated hepatocytes undergo a tremendous proliferative process. CREM gene exp
ression 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. C
REM mutation results in delayed S-phase entry, impairing the synchronizatio
n of proliferation.