title: NF-Y binds to both G1- and G2-specific cyclin promoters; a possible role in linking CDK2/Cyclin A to CDK1/Cyclin B.
abstract: We previously reported that CDK2/Cyclin A can phosphorylate and activate the transcription factor NF-Y. In this study, we investigated a potential regulatory role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the Cyclin A promoter, as well as to those in the promoters of cell cycle G2 regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however, Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of CDK2/Cyclin A. These results suggest a model wherein NF-Y binds to and activates transcription from the Cyclin A promoter, increasing cellular levels of Cyclin A/CDK2 and potentiating NF-Y's capacity for transcriptional transactivation, and imply a positive feedback loop between NF-Y and Cyclin A/CDK2. Our findings are additionally indicative of a role for Cyclin A in activating Cyclin B/CDK1 through promoting NF-Y dependent transcription of Cyclin B and CDC2; NF-Y mediated crosstalk may therefore help to orchestrate cell-cycle progression.
authors.affiliation: Department of Microbiology, Dankook University College of Medicine, Cheonan, Korea.
authors.forename: Hee-Don
authors.initials: HD
authors.lastname: Chae
authors.forename: Jungbin
authors.initials: J
authors.lastname: Kim
authors.forename: Deug Y
authors.initials: DY
authors.lastname: Shin
mesh_terms: D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D025461:Feedback, Physiological; D016193:G1 Phase; D016195:G2 Phase; D056945:Hep G2 Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding
chemical_list: D023081:CCAAT-Binding Factor; D019925:Cyclin A; D019926:Cyclin B; D016213:Cyclins; C402244:nuclear factor Y; D004247:DNA; D016203:CDC2 Protein Kinase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2