Recovery of liver mass without proliferation of hepatocytes after partial hepatectomy in Skp2-deficient mice.
The abundance of p27(Kip1), an inhibitor of cell proliferation, is determined by Skp2-dependent proteolysis, the deregulation of which is associated with cancer progression. Lack of Skp2 results in p27(Kip1) accumulation as well as enlargement and polyploidy of hepatocytes. The role of Skp2 in cell growth and proliferation was investigated in Skp2-deficient mice subjected to partial hepatectomy. Skp2(-/-) mice exhibited restoration of liver mass without cell proliferation; rather, hepatocytes increased in size, an effect that was accompanied by increased polyploidy and p27(Kip1) accumulation. Lack of Skp2 thus impairs hepatocyte proliferation, which is compensated for by cellular enlargement, during liver regeneration.
Minamishima
Yohji A
YA
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
Nakayama
Keiko
K
Nakayama
Kei-Ichi
K
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008938:Mitosis / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D011003:Ploidies; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27