Cyclin-dependent kinase activation and S-phase induction of the cyclin B1 gene are linked through the CCAAT elements.
Control of cell proliferation is dependent on the regulated expression of the cyclin genes. Induction of cyclin B1 gene expression in S phase has been shown to require sequences within the first 90 bp of the proximal promoter region. In this study, we defined the cell cycle regulatory elements within this region and explored the mechanism by which the cyclin B1 gene is activated. A CDE-like element that is important in S-phase regulation of other genes was not required for correct cell cycle expression of cyclin B1. Instead, two CCAAT boxes were essential for S-phase induction of cyclin B1 gene in both NIH3T3 and HeLa cells. Induction of cyclin B1 by cyclin/cyclin-dependent kinase (cdk) complexes were examined by cotransfection of the reporter along with appropriate expression vectors. Complexes of cdk4 with cyclin D1 or cdk2 with cyclin E or A can activate the cyclin B1 promoter, and activation is uniquely dependent on the CCAAT elements in both normal and heterologous contexts. This transcription factor NF-Y binds to both CCAAT elements. These findings suggest that S phase-specific induction of the cyclin B1 promoter is dependent upon NF-Y binding to the CCAAT elements and is correlated with activation by cyclin-dependent kinases.
Katula
K S
KS
Department of Biology, University of North Carolina at Greensboro 27412, USA.
Wright
K L
KL
Paul
H
H
Surman
D R
DR
Nuckolls
F J
FJ
Smith
J W
JW
Ting
J P
JP
Yates
J
J
Cogswell
J P
JP
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D042846:CDC2-CDC28 Kinases; D019926:Cyclin B; D056744:Cyclin B1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016196:S Phase / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; 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