A potential role for p15(Ink4b) and p57(Kip2) in liver development.
Hepatocytes undergo marked changes in proliferation during normal liver development. In order to elucidate the mechanism for these changes, we examined the ontogeny of expression for the known cyclin-dependent kinase inhibitors (CKIs), p15(Ink4b), p16(Ink4a), p18(Ink4c), p19(Ink4d), p21(Cip1), p27(Kip1) and p57(Kip2). All except p16(Ink4a) were expressed at some time between late gestation and adulthood. The mRNA and protein expression patterns for p15(Ink4b) and p57(Kip2) were consistent with a role for these CKIs in the regulation of hepatocyte proliferation. Specifically, p57(Kip2) may contribute to hepatocyte growth arrest that occurs in term fetuses, while p15(Ink4b) may contribute to the maintenance of adult hepatocytes in a quiescent state. These results assign a possible role to two CKIs not previously identified as involved in hepatocyte cell cycle control.
Awad
M M
MM
Department of Pediatrics, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA.
Sanders
J A
JA
Gruppuso
P A
PA
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; C493969:Cdkn2b protein, rat; C493973:Cdkn2c protein, rat; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012313:RNA; D018844:Cyclin-Dependent Kinases