title: p57(Kip2) regulates the proper development of labyrinthine and spongiotrophoblasts.
abstract: The cyclin-dependent kinase (cdk) inhibitor, p57 (Kip2) is a tumour suppressor candidate and a paternally-imprinted gene. In humans, the p57(Kip2) gene is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome. From analysis of p57(Kip2)-deficient mice, we demonstrate the relationship between trophoblastic abnormalities and p57(Kip2). Both p57(Kip2) null ((-/-)) embryos and heterozygous embryos with a maternally-derived mutated allele ((+*/-)) displayed placentomegaly, as well as dysplasia of labyrinthine and spongiotrophoblasts. The number of labyrinthine trophoblasts of homozygous embryos was twice that in wild-type embryos. When we measured kinase activities of cdk in total placenta lysates by the immuno complex kinase assay, there were no differences among the genotypes. These results show that p57(Kip2) may function in the proper development of labyrinthine and spongiotrophoblasts by pathways that are not involved with regulation of cdk activities. It is, therefore, suggested that p57(Kip2) protein might have an unknown role.
authors.affiliation: Molecular Oncology Group, Nippon Roche Research Center 200, Kajiwara, Kamakura, Kanagawa 247-8530, Japan. takahask@pharm.showa-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Kanayama
mesh_terms: D000818:Animals; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000002:abnormalities / Q000473:pathology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D014327:Trophoblasts / Q000473:pathology / Q000502:physiology*
chemical_list: C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases