G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK complexes.
WT1, the Wilms tumor-suppressor gene, maps to the human chromosomal region 11p13 and encodes a transcriptional repressor, WT1, implicated in controlling normal urogenital development. Microinjection of the WT1 cDNA into quiescent cells or cells in early to mid G1 phase blocked serum-induced cell cycle progression into S phase. The activity of WT1 varied significantly depending on the presence or absence of an alternatively spliced region located upstream of the zinc finger domain. The inhibitory activity of WT1 was abrogated by the overexpression of cyclin E/CDK2 as well as cyclin D1/CDK4. Furthermore, both CDK4- and CDK2-associated kinase activities were downregulated in cells overexpressing WT1, whereas the levels of CDK4, CDK2, and cyclin D1 expression were unchanged. These findings suggest that inhibition of the activity of cyclin/CDK complexes may be involved in mediating the WT1-induced cell cycle block.
Kudoh
T
T
Department of Oncogene Research, Osaka University, Japan.
Ishidate
T
T
Moriyama
M
M
Toyoshima
K
K
Akiyama
T
T
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase; D015870:Gene Expression; D016162:Genes, Wilms Tumor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection; D025721:WT1 Proteins
D016213:Cyclins; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases