NF-Y Mediates the Transcriptional Inhibition of thecyclin B1, cyclin B2, and cdc25CPromoters upon Induced G2 Arrest

Abstract

During normal cell cycles, the function of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, is required for G2 phase progression. Accordingly, the G2 arrest induced by DNA damage is associated with a down-regulation of mitotic cyclins, cdk1, and cdc25C phosphatase expression. We found that the promoter activity of these genes is repressed in the G2 arrest induced by DNA damage. We asked whether the CCAAT-binding NF-Y modulates mitoticcyclins, cdk1, and cdc25C gene transcription during this type of G2 arrest. In our experimental conditions, the integrity of the CCAAT boxes ofcyclin B1, cyclin B2, and cdc25Cpromoters, as well as the presence of a functional NF-Y complex, is strictly required for the transcriptional inhibition of these promoters. Furthermore, a dominant-negative p53 protein, impairing doxorubicin-induced G2 arrest, prevents transcriptional down-regulation of the mitotic cyclins, cdk1, and cdc25C genes. We conclude that, as already demonstrated for cdk1, NF-Y mediates the transcriptional inhibition of the mitotic cyclins and the cdc25C genes during p53-dependent G2 arrest induced by DNA damage. These data suggest a transcriptional regulatory role of NF-Y in the G2 checkpoint after DNA damage. During normal cell cycles, the function of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, is required for G2 phase progression. Accordingly, the G2 arrest induced by DNA damage is associated with a down-regulation of mitotic cyclins, cdk1, and cdc25C phosphatase expression. We found that the promoter activity of these genes is repressed in the G2 arrest induced by DNA damage. We asked whether the CCAAT-binding NF-Y modulates mitoticcyclins, cdk1, and cdc25C gene transcription during this type of G2 arrest. In our experimental conditions, the integrity of the CCAAT boxes ofcyclin B1, cyclin B2, and cdc25Cpromoters, as well as the presence of a functional NF-Y complex, is strictly required for the transcriptional inhibition of these promoters. Furthermore, a dominant-negative p53 protein, impairing doxorubicin-induced G2 arrest, prevents transcriptional down-regulation of the mitotic cyclins, cdk1, and cdc25C genes. We conclude that, as already demonstrated for cdk1, NF-Y mediates the transcriptional inhibition of the mitotic cyclins and the cdc25C genes during p53-dependent G2 arrest induced by DNA damage. These data suggest a transcriptional regulatory role of NF-Y in the G2 checkpoint after DNA damage. nuclear factor Y Adriamycin phosphate-buffered saline chloramphenicol acetyltransferase luciferase cytomegalovirus In mammalian cells, progression through the G2 phase of the cell cycle is mediated by the activity of a specific set of proteins, which includes mitotic cyclins A, B1, and B2, mitotic kinase cdk1 (alias p34cdc2), and mitotic phosphatase cdc25C. The kinase activity of cdk1 during the G2 phase is dependent on its dephosphorylated status of specific residues triggered by the phosphatase activity of cdc25C protein (1Gould K.L. Nurse P. Nature. 1989; 342: 39-45Crossref PubMed Scopus (851) Google Scholar, 2Pines J. Hunter T. Cell. 1989; 58: 833-846Abstract Full Text PDF PubMed Scopus (693) Google Scholar, 3Pines J. Hunter T. Nature. 1990; 346: 760-763Crossref PubMed Scopus (528) Google Scholar, 4Parker L.L. Piwnica-Worms H. Science. 1992; 257: 1955-1957Crossref PubMed Scopus (536) Google Scholar, 5McGowan C.H. Russell P. EMBO J. 1993; 12: 75-85Crossref PubMed Scopus (384) Google Scholar, 6Liu F. Stanton J.J. Wu Z. Piwnica-Worms H. Mol. Cell. Biol. 1997; 17: 571-583Crossref PubMed Scopus (263) Google Scholar), as well as on the levels of cyclins A and Bs. In proliferating cells, oscillations of mitotic cyclin amounts are tightly regulated at the transcriptional level (7Henglein B. Chenivesse X. Wang J. Eick D. Brechot C. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 5490-5494Crossref PubMed Scopus (244) Google Scholar, 8Hwang A. Maity A. McKenna W.G. Muschel R.J. J. Biol. Chem. 1995; 270: 28419-28424Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 9Lucibello F.C. Truss M. Zwicker J. Ehlert F. Beato M. Muller R. EMBO J. 1995; 14: 132-142Crossref PubMed Scopus (87) Google Scholar, 10Piaggio G. Farina A. Perrotti D. Manni I. Fuschi P. Sacchi A. Gaetano C. Exp. Cell Res. 1995; 216: 396-402Crossref PubMed Scopus (54) Google Scholar, 11Zwicker J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, 12Katula K.S. Wright K.L. Paul H. Surman D.R. Nuckolls F.J. Smith J.W. Ting J.P. Yates J. Cogswell J.P. Cell Growth Differ. 1997; 8: 11-20PubMed Google Scholar). In particular, activation of cdk1 does not occur until sufficient cyclin B1 protein is synthesized (13Solomon M.J. Glotzer M. Lee H. Philipe M. Kirshner S. Cell. 1990; 63: 1013-1034Abstract Full Text PDF PubMed Scopus (503) Google Scholar). The accumulation of mitotic cyclins and cdk1 correlates with nascent gene expression, and their mRNAs can only be detected in particular phases of the cell cycle (2Pines J. Hunter T. Cell. 1989; 58: 833-846Abstract Full Text PDF PubMed Scopus (693) Google Scholar, 7Henglein B. Chenivesse X. Wang J. Eick D. Brechot C. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 5490-5494Crossref PubMed Scopus (244) Google Scholar, 10Piaggio G. Farina A. Perrotti D. Manni I. Fuschi P. Sacchi A. Gaetano C. Exp. Cell Res. 1995; 216: 396-402Crossref PubMed Scopus (54) Google Scholar, 14Dalton S. EMBO J. 1992; 11: 797-1804Crossref Scopus (335) Google Scholar).Cell cycle progression through the G2 phase is controlled by the G2 checkpoint. This checkpoint ensures correct DNA synthesis during cell proliferation and genome integrity after DNA damage. In the latter condition, cells can arrest at the G1and/or the G2 checkpoint, depending on cell type, cell cycle phase, and checkpoint integrity (15Kastan M.B. Onyekwere O. Sidransky D. Vogelstein B. Craig R.W. Cancer Res. 1991; 51: 6304-6311PubMed Google Scholar, 16Maity A. McKenna W.G. Muschel R.J. Radiother. Oncol. 1994; 31: 1-13Abstract Full Text PDF PubMed Scopus (270) Google Scholar, 17Cox L.S. Lane D.P. Bioessays. 1995; 17: 501-508Crossref PubMed Scopus (310) Google Scholar). The G1/G2 arrest after DNA damage is regulated, at in by the of the cells, for the G2 the phase and DNA of of F. A. C. T. S. J.P. Vogelstein B. Science. PubMed Scopus Google Scholar). of type p53 associated with down-regulation of cyclin B1, cyclin A, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, Lee Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). In with these that type p53 in cells can the transcriptional activity of cyclin B1, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. M. K. T. T. T. Exp. Cell Res. 1994; PubMed Scopus Google Scholar, T. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the specific for the down-regulation of the transcription of these genes in the G2 arrest are CCAAT is in of the of and cell of genes P. J. Mol. Biol. 1990; PubMed Scopus Google Scholar). R. Nucleic Acids Res. PubMed Scopus Google Scholar). is of and genes in and R. D. H. C. D. EMBO J. 1990; Scopus Google Scholar, R. R. C. Biol. Chem. 1992; Full Text PDF Google Scholar, 1995; PubMed Scopus Google Scholar, S. Maity B. Proc. Natl. Acad. Sci. U. S. A. 1995; PubMed Scopus Google Scholar, M. K. Farina A. J. G. R. 1997; Google Scholar). are required for CCAAT G. R. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar). The of cyclin A, cyclin B1, cyclin and cdc25C genes CCAAT and demonstrated that NF-Y at in their activity during the cell cycle J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar, F. M. C. A. A. Muller H. Manni I. J. G. R. Engeland K. PubMed Scopus Google Scholar). asked whether NF-Y is in the of these promoter during the G2 arrest induced by DNA this induced a G2 arrest by DNA damage in cells, which a type p53 S. G. R. S. A. G. M. Sacchi A. J. Cell Biol. PubMed Scopus Google Scholar). We found that the promoter of the mitoticcyclins, cdk1, and cdc25C genes. This down-regulation a at in the CCAAT boxes and the transcription factor a dominant-negative p53 protein that the down-regulation of mitoticcyclins, cdk1, and cdc25C only in the presence of a functional p53 progression through the G2 phase of the cell cycle is regulated in by the cyclin and cyclin mitotic J. Hunter T. Biol. 1990; Google Scholar, M. R. F. G. EMBO J. 1992; 11: PubMed Scopus Google Scholar). that after DNA damage the mitotic is F. A. C. T. S. J.P. Vogelstein B. Science. PubMed Scopus Google Scholar, Mol. Cell. Biol. PubMed Scopus Google Scholar, P. S. Cell Growth Differ. Scholar), the the G2 arrest is not In this that during the G2 arrest, a of protein levels of cyclin A, cyclin B1, cdk1, and cdc25C at in by a transcriptional level of is that after the promoter of A, cyclin B1, cyclin and cdc25C genes are These that that in the normal cell cycle are during the G2 checkpoint induced by DNA of cyclin B1, cyclin B2, in the G2 arrest, the integrity of the CCAAT boxes in the of these a role for the transcription factor NF-Y and demonstrated that NF-Y the CCAAT boxes of cyclin B1, cyclin B2, J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar, F. M. C. A. A. Muller H. Manni I. J. G. R. Engeland K. PubMed Scopus Google Scholar). that a functional NF-Y is required for the inhibition of cyclin B1, cyclin B2, and cdc25C during G2 arrest. the of a dominant-negative the of these promoters. as already this is for promoter J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google down-regulation of and transcription of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, after DNA damage the presence of a functional p53 protein In with this that of p53 in cells the transcriptional activity of cyclin A, cyclin B1, cyclin B2, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. M. K. T. T. T. Exp. Cell Res. 1994; PubMed Scopus Google Scholar, T. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. M. U. C. J. Engeland K. Nucleic Acids Res. PubMed Scopus Google Scholar). this is the that the cdc25C promoter activity is of the a DNA for our the that p53 with the function of that p53 protein can transcription by and the function of specific transcription G. P. J. C. Nucleic Acids Res. PubMed Scopus Google Scholar, C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In with NF-Y that NF-Y is on the CCAAT boxes of cyclin B1 and cyclin and after p53 does not with the DNA of is that p53 with the NF-Y of transcription that p53 and NF-Y of the K. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M. EMBO J. 17: PubMed Scopus Google Scholar), and p53 and NF-Y protein G. J. C. Mol. Cell. Biol. PubMed Google Scholar, M. Lee K. R. Nucleic Acids Res. 1997; PubMed Scopus Google NF-Y by be required for the inhibition of cdk1 transcription A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, NF-Y the CCAAT in the cyclin A promoter J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar). These the that NF-Y modulates cdk1 and cyclin A transcription after G2 arrest by the for the cyclin B1, cyclin B2, that p53 protein a G2 arrest induced by through a of cyclin B1 and cdk1 Mol. Cell. Biol. PubMed Scopus Google Scholar). the inhibition of cyclin B1 does not be by of the cyclin B1 as by does not cells, the cyclin B1 The transcriptional of the of mitotic kinase is not the only that a demonstrated that in a cell the p53-dependent G2 arrest after is the of of H. C. K. S. Vogelstein B. Mol. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). the cell cycle the nuclear of B1 and cdc25C phosphatase H. C. Vogelstein B. Nature. PubMed Scopus Google Scholar). after DNA transcriptional down-regulation of mitotic kinase and their M. EMBO J. 17: PubMed Scopus Google the G2 this that in cells, the for the G2 checkpoint induced by DNA damage the of the NF-Y transcription factor the transcription of regulatory for the progression through the of the cell This the of whether controlled by NF-Y during the cell cycle R. Nucleic Acids Res. PubMed Scopus Google Scholar), are of its activity in the cell cycle In mammalian cells, progression through the G2 phase of the cell cycle is mediated by the activity of a specific set of proteins, which includes mitotic cyclins A, B1, and B2, mitotic kinase cdk1 (alias p34cdc2), and mitotic phosphatase cdc25C. The kinase activity of cdk1 during the G2 phase is dependent on its dephosphorylated status of specific residues triggered by the phosphatase activity of cdc25C protein (1Gould K.L. Nurse P. Nature. 1989; 342: 39-45Crossref PubMed Scopus (851) Google Scholar, 2Pines J. Hunter T. Cell. 1989; 58: 833-846Abstract Full Text PDF PubMed Scopus (693) Google Scholar, 3Pines J. Hunter T. Nature. 1990; 346: 760-763Crossref PubMed Scopus (528) Google Scholar, 4Parker L.L. Piwnica-Worms H. Science. 1992; 257: 1955-1957Crossref PubMed Scopus (536) Google Scholar, 5McGowan C.H. Russell P. EMBO J. 1993; 12: 75-85Crossref PubMed Scopus (384) Google Scholar, 6Liu F. Stanton J.J. Wu Z. Piwnica-Worms H. Mol. Cell. Biol. 1997; 17: 571-583Crossref PubMed Scopus (263) Google Scholar), as well as on the levels of cyclins A and Bs. In proliferating cells, oscillations of mitotic cyclin amounts are tightly regulated at the transcriptional level (7Henglein B. Chenivesse X. Wang J. Eick D. Brechot C. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 5490-5494Crossref PubMed Scopus (244) Google Scholar, 8Hwang A. Maity A. McKenna W.G. Muschel R.J. J. Biol. Chem. 1995; 270: 28419-28424Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 9Lucibello F.C. Truss M. Zwicker J. Ehlert F. Beato M. Muller R. EMBO J. 1995; 14: 132-142Crossref PubMed Scopus (87) Google Scholar, 10Piaggio G. Farina A. Perrotti D. Manni I. Fuschi P. Sacchi A. Gaetano C. Exp. Cell Res. 1995; 216: 396-402Crossref PubMed Scopus (54) Google Scholar, 11Zwicker J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, 12Katula K.S. Wright K.L. Paul H. Surman D.R. Nuckolls F.J. Smith J.W. Ting J.P. Yates J. Cogswell J.P. Cell Growth Differ. 1997; 8: 11-20PubMed Google Scholar). In particular, activation of cdk1 does not occur until sufficient cyclin B1 protein is synthesized (13Solomon M.J. Glotzer M. Lee H. Philipe M. Kirshner S. Cell. 1990; 63: 1013-1034Abstract Full Text PDF PubMed Scopus (503) Google Scholar). The accumulation of mitotic cyclins and cdk1 correlates with nascent gene expression, and their mRNAs can only be detected in particular phases of the cell cycle (2Pines J. Hunter T. Cell. 1989; 58: 833-846Abstract Full Text PDF PubMed Scopus (693) Google Scholar, 7Henglein B. Chenivesse X. Wang J. Eick D. Brechot C. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 5490-5494Crossref PubMed Scopus (244) Google Scholar, 10Piaggio G. Farina A. Perrotti D. Manni I. Fuschi P. Sacchi A. Gaetano C. Exp. Cell Res. 1995; 216: 396-402Crossref PubMed Scopus (54) Google Scholar, 14Dalton S. EMBO J. 1992; 11: 797-1804Crossref Scopus (335) Google Scholar). Cell cycle progression through the G2 phase is controlled by the G2 checkpoint. This checkpoint ensures correct DNA synthesis during cell proliferation and genome integrity after DNA damage. In the latter condition, cells can arrest at the G1and/or the G2 checkpoint, depending on cell type, cell cycle phase, and checkpoint integrity (15Kastan M.B. Onyekwere O. Sidransky D. Vogelstein B. Craig R.W. Cancer Res. 1991; 51: 6304-6311PubMed Google Scholar, 16Maity A. McKenna W.G. Muschel R.J. Radiother. Oncol. 1994; 31: 1-13Abstract Full Text PDF PubMed Scopus (270) Google Scholar, 17Cox L.S. Lane D.P. Bioessays. 1995; 17: 501-508Crossref PubMed Scopus (310) Google Scholar). The G1/G2 arrest after DNA damage is regulated, at in by the of the cells, for the G2 the phase and DNA of of F. A. C. T. S. J.P. Vogelstein B. Science. PubMed Scopus Google Scholar). of type p53 associated with down-regulation of cyclin B1, cyclin A, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, Lee Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). In with these that type p53 in cells can the transcriptional activity of cyclin B1, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. M. K. T. T. T. Exp. Cell Res. 1994; PubMed Scopus Google Scholar, T. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the specific for the down-regulation of the transcription of these genes in the G2 arrest are The CCAAT is in of the of and cell of genes P. J. Mol. Biol. 1990; PubMed Scopus Google Scholar). R. Nucleic Acids Res. PubMed Scopus Google Scholar). is of and genes in and R. D. H. C. D. EMBO J. 1990; Scopus Google Scholar, R. R. C. Biol. Chem. 1992; Full Text PDF Google Scholar, 1995; PubMed Scopus Google Scholar, S. Maity B. Proc. Natl. Acad. Sci. U. S. A. 1995; PubMed Scopus Google Scholar, M. K. Farina A. J. G. R. 1997; Google Scholar). are required for CCAAT G. R. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar). The of cyclin A, cyclin B1, cyclin and cdc25C genes CCAAT and demonstrated that NF-Y at in their activity during the cell cycle J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar, F. M. C. A. A. Muller H. Manni I. J. G. R. Engeland K. PubMed Scopus Google Scholar). asked whether NF-Y is in the of these promoter during the G2 arrest induced by DNA damage. this induced a G2 arrest by DNA damage in cells, which a type p53 S. G. R. S. A. G. M. Sacchi A. J. Cell Biol. PubMed Scopus Google Scholar). We found that the promoter of the mitoticcyclins, cdk1, and cdc25C genes. This down-regulation a at in the CCAAT boxes and the transcription factor a dominant-negative p53 protein that the down-regulation of mitoticcyclins, cdk1, and cdc25C only in the presence of a functional p53 progression through the G2 phase of the cell cycle is regulated in by the cyclin and cyclin mitotic J. Hunter T. Biol. 1990; Google Scholar, M. R. F. G. EMBO J. 1992; 11: PubMed Scopus Google Scholar). that after DNA damage the mitotic is F. A. C. T. S. J.P. Vogelstein B. Science. PubMed Scopus Google Scholar, Mol. Cell. Biol. PubMed Scopus Google Scholar, P. S. Cell Growth Differ. Scholar), the the G2 arrest is not In this that during the G2 arrest, a of protein levels of cyclin A, cyclin B1, cdk1, and cdc25C at in by a transcriptional level of is that after the promoter of A, cyclin B1, cyclin and cdc25C genes are These that that in the normal cell cycle are during the G2 checkpoint induced by DNA of cyclin B1, cyclin B2, in the G2 arrest, the integrity of the CCAAT boxes in the of these a role for the transcription factor NF-Y and demonstrated that NF-Y the CCAAT boxes of cyclin B1, cyclin B2, J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar, F. M. C. A. A. Muller H. Manni I. J. G. R. Engeland K. PubMed Scopus Google Scholar). that a functional NF-Y is required for the inhibition of cyclin B1, cyclin B2, and cdc25C during G2 arrest. the of a dominant-negative the of these promoters. as already this is for promoter J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google down-regulation of and transcription of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, after DNA damage the presence of a functional p53 protein In with this that of p53 in cells the transcriptional activity of cyclin A, cyclin B1, cyclin B2, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. M. K. T. T. T. Exp. Cell Res. 1994; PubMed Scopus Google Scholar, T. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. M. U. C. J. Engeland K. Nucleic Acids Res. PubMed Scopus Google Scholar). this is the that the cdc25C promoter activity is of the a DNA for our the that p53 with the function of that p53 protein can transcription by and the function of specific transcription G. P. J. C. Nucleic Acids Res. PubMed Scopus Google Scholar, C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In with NF-Y that NF-Y is on the CCAAT boxes of cyclin B1 and cyclin and after p53 does not with the DNA of is that p53 with the NF-Y of transcription that p53 and NF-Y of the K. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M. EMBO J. 17: PubMed Scopus Google Scholar), and p53 and NF-Y protein G. J. C. Mol. Cell. Biol. PubMed Google Scholar, M. Lee K. R. Nucleic Acids Res. 1997; PubMed Scopus Google NF-Y by be required for the inhibition of cdk1 transcription A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, NF-Y the CCAAT in the cyclin A promoter J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar). These the that NF-Y modulates cdk1 and cyclin A transcription after G2 arrest by the for the cyclin B1, cyclin B2, that p53 protein a G2 arrest induced by through a of cyclin B1 and cdk1 Mol. Cell. Biol. PubMed Scopus Google Scholar). the inhibition of cyclin B1 does not be by of the cyclin B1 as by does not cells, the cyclin B1 The transcriptional of the of mitotic kinase is not the only that a demonstrated that in a cell the p53-dependent G2 arrest after is the of of H. C. K. S. Vogelstein B. Mol. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). the cell cycle the nuclear of B1 and cdc25C phosphatase H. C. Vogelstein B. Nature. PubMed Scopus Google Scholar). after DNA transcriptional down-regulation of mitotic kinase and their M. EMBO J. 17: PubMed Scopus Google the G2 this that in cells, the for the G2 checkpoint induced by DNA damage the of the NF-Y transcription factor the transcription of regulatory for the progression through the of the cell This the of whether controlled by NF-Y during the cell cycle R. Nucleic Acids Res. PubMed Scopus Google Scholar), are of its activity in the cell cycle The progression through the G2 phase of the cell cycle is regulated in by the cyclin and cyclin mitotic J. Hunter T. Biol. 1990; Google Scholar, M. R. F. G. EMBO J. 1992; 11: PubMed Scopus Google Scholar). that after DNA damage the mitotic is F. A. C. T. S. J.P. Vogelstein B. Science. PubMed Scopus Google Scholar, Mol. Cell. Biol. PubMed Scopus Google Scholar, P. S. Cell Growth Differ. Scholar), the the G2 arrest is not In this that during the G2 arrest, a of protein levels of cyclin A, cyclin B1, cdk1, and cdc25C at in by a transcriptional level of is that after the promoter of A, cyclin B1, cyclin and cdc25C genes are These that that in the normal cell cycle are during the G2 checkpoint induced by DNA damage. The of cyclin B1, cyclin B2, in the G2 arrest, the integrity of the CCAAT boxes in the of these a role for the transcription factor NF-Y and demonstrated that NF-Y the CCAAT boxes of cyclin B1, cyclin B2, J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar, A. Manni I. G. M. C. M. R. Sacchi A. G. PubMed Scopus Google Scholar, F. M. C. A. A. Muller H. Manni I. J. G. R. Engeland K. PubMed Scopus Google Scholar). that a functional NF-Y is required for the inhibition of cyclin B1, cyclin B2, and cdc25C during G2 arrest. the of a dominant-negative the of these promoters. as already this is for promoter J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The down-regulation of and transcription of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, after DNA damage the presence of a functional p53 protein In with this that of p53 in cells the transcriptional activity of cyclin A, cyclin B1, cyclin B2, and cdk1 Cogswell J.P. Lee Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. M. K. T. T. T. Exp. Cell Res. 1994; PubMed Scopus Google Scholar, T. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. M. U. C. J. Engeland K. Nucleic Acids Res. PubMed Scopus Google Scholar). this is the that the cdc25C promoter activity is of the a DNA for our the that p53 with the function of that p53 protein can transcription by and the function of specific transcription G. P. J. C. Nucleic Acids Res. PubMed Scopus Google Scholar, C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In with NF-Y that NF-Y is on the CCAAT boxes of cyclin B1 and cyclin and after p53 does not with the DNA of is that p53 with the NF-Y of transcription that p53 and NF-Y of the K. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M. EMBO J. 17: PubMed Scopus Google Scholar), and p53 and NF-Y protein G. J. C. Mol. Cell. Biol. PubMed Google Scholar, M. Lee K. R. Nucleic Acids Res. 1997; PubMed Scopus Google Scholar). NF-Y by be required for the inhibition of cdk1 transcription A. K.S. Mol. Biol. Cell. PubMed Scopus Google Scholar, J. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, NF-Y the CCAAT in the cyclin A promoter J. Gross C. Lucibello F.C. Truss M. Ehlert F Engeland K. Muller R. Nucleic Acids Res. 1995; 23: 3822-3830Crossref PubMed Scopus (91) Google Scholar). These the that NF-Y modulates cdk1 and cyclin A transcription after G2 arrest by the for the cyclin B1, cyclin B2, genes. that p53 protein a G2 arrest induced by through a of cyclin B1 and cdk1 Mol. Cell. Biol. PubMed Scopus Google Scholar). the inhibition of cyclin B1 does not be by of the cyclin B1 as by does not cells, the cyclin B1 The transcriptional of the of mitotic kinase is not the only that a demonstrated that in a cell the p53-dependent G2 arrest after is the of of H. C. K. S. Vogelstein B. Mol. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). the cell cycle the nuclear of B1 and cdc25C phosphatase H. C. Vogelstein B. Nature. PubMed Scopus Google Scholar). after DNA transcriptional down-regulation of mitotic kinase and their M. 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