Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hateboer, G.
	Articles by Helin, K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hateboer, G.
	Articles by Helin, K.

Previous Article | Next Article

Molecular and Cellular Biology, November 1998, p. 6679-6697, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F

Guus Hateboer,¹^, Albrecht Wobst,¹ Birgit Otzen Petersen,¹ Laurent Le Cam,² Elena Vigo,¹ Claude Sardet,² and Kristian Helin¹^,^*

Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy,¹ and Institut de Génétique Moléculaire, CNRM, UMR 5535, 34033 Montpellier Cedex 1, France²

Received 20 February 1998/Returned for modification 13 April 1998/Accepted 18 August 1998

The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expressionof a number of genes whose products are involved in DNA replicationand cell proliferation. In Saccharomyces cerevisiae, the MBF andSBF transcription complexes have functions similar to those ofE2F proteins in higher eukaryotes, by regulating the timed expressionof genes implicated in cell cycle progression and DNA synthesis.The CDC6 gene is a target for MBF and SBF-regulated transcription.S. cerevisiae Cdc6p induces the formation of the prereplicationcomplex and is essential for initiation of DNA replication. Interestingly,the Cdc6p homolog in Schizosaccharomyces pombe, Cdc18p, is regulatedby DSC1, the S. pombe homolog of MBF. By cloning the promoterfor the human homolog of Cdc6p and Cdc18p, we demonstrate herethat the cell cycle-regulated transcription of this gene is dependenton E2F. In vivo footprinting data demonstrate that the identifiedE2F sites are occupied in resting cells and in exponentially growingcells, suggesting that E2F is responsible for downregulating thepromoter in early phases of the cell cycle and the subsequentupregulation when cells enter S phase. Our data also demonstratethat the human CDC6 protein (hCDC6) is essential and limitingfor DNA synthesis, since microinjection of an anti-CDC6 rabbitantiserum blocks DNA synthesis and CDC6 cooperates with cyclinE to induce entry into S phase in cotransfection experiments.Furthermore, E2F is sufficient to induce expression of the endogenousCDC6 gene even in the absence of de novo protein synthesis. Inconclusion, our results provide a direct link between regulatedprogression through G₁ controlled by the pRB pathway and the expressionof proteins essential for the initiation of DNA replication.

^* Corresponding author. Mailing address: Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti435, 20141 Milan, Italy. Phone: 39 02 5748 9860. Fax: 39 02 57489851. E-mail: khelin{at}ieo.cilea.it.

Present address: IntroGene, 2333 AL Leiden, The Netherlands.

Molecular and Cellular Biology, November 1998, p. 6679-6697, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Borlado, L. R., Mendez, J. (2008). CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis 29: 237-243 [Abstract] [Full Text]
Hall, J. R., Kow, E., Nevis, K. R., Lu, C. K., Luce, K. S., Zhong, Q., Cook, J. G. (2007). Cdc6 Stability Is Regulated by the Huwe1 Ubiquitin Ligase after DNA Damage. Mol. Biol. Cell 18: 3340-3350 [Abstract] [Full Text]
Braun, K. A., Breeden, L. L. (2007). Nascent Transcription of MCM2-7 Is Important for Nuclear Localization of the Minichromosome Maintenance Complex in G1. Mol. Biol. Cell 18: 1447-1456 [Abstract] [Full Text]
El Messaoudi, S., Fabbrizio, E., Rodriguez, C., Chuchana, P., Fauquier, L., Cheng, D., Theillet, C., Vandel, L., Bedford, M. T., Sardet, C. (2006). Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene. Proc. Natl. Acad. Sci. USA 103: 13351-13356 [Abstract] [Full Text]
Christensen, J., Cloos, P., Toftegaard, U., Klinkenberg, D., Bracken, A. P., Trinh, E., Heeran, M., Di Stefano, L., Helin, K. (2005). Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription. Nucleic Acids Res 33: 5458-5470 [Abstract] [Full Text]
Berteaux, N., Lottin, S., Monte, D., Pinte, S., Quatannens, B., Coll, J., Hondermarck, H., Curgy, J.-J., Dugimont, T., Adriaenssens, E. (2005). H19 mRNA-like Noncoding RNA Promotes Breast Cancer Cell Proliferation through Positive Control by E2F1. J. Biol. Chem. 280: 29625-29636 [Abstract] [Full Text]
Duursma, A., Agami, R. (2005). p53-Dependent Regulation of Cdc6 Protein Stability Controls Cellular Proliferation. Mol. Cell. Biol. 25: 6937-6947 [Abstract] [Full Text]
Fujii-Yamamoto, H., Kim, J. M., Arai, K.-i., Masai, H. (2005). Cell Cycle and Developmental Regulations of Replication Factors in Mouse Embryonic Stem Cells. J. Biol. Chem. 280: 12976-12987 [Abstract] [Full Text]
Vilaboa, N., Bermejo, R., Martinez, P., Bornstein, R., Cales, C. (2004). A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization. Nucleic Acids Res 32: 6454-6467 [Abstract] [Full Text]
Karakaidos, P., Taraviras, S., Vassiliou, L. V., Zacharatos, P., Kastrinakis, N. G., Kougiou, D., Kouloukoussa, M., Nishitani, H., Papavassiliou, A. G., Lygerou, Z., Gorgoulis, V. G. (2004). Overexpression of the Replication Licensing Regulators hCdt1 and hCdc6 Characterizes a Subset of Non-Small-Cell Lung Carcinomas: Synergistic Effect with Mutant p53 on Tumor Growth and Chromosomal Instability--Evidence of E2F-1 Transcriptional Control over hCdt1. Am. J. Pathol. 165: 1351-1365 [Abstract] [Full Text]
Shestakova, E. A., Mansuroglu, Z., Mokrani, H., Ghinea, N., Bonnefoy, E. (2004). Transcription factor YY1 associates with pericentromeric {gamma}-satellite DNA in cycling but not in quiescent (G0) cells. Nucleic Acids Res 32: 4390-4399 [Abstract] [Full Text]
Lea, N. C., Orr, S. J., Stoeber, K., Williams, G. H., Lam, E. W.-F., Ibrahim, M. A. A., Mufti, G. J., Thomas, N. S. B. (2003). Commitment Point during G0->G1 That Controls Entry into the Cell Cycle. Mol. Cell. Biol. 23: 2351-2361 [Abstract] [Full Text]
Biswas, N., Sanchez, V., Spector, D. H. (2003). Human Cytomegalovirus Infection Leads to Accumulation of Geminin and Inhibition of the Licensing of Cellular DNA Replication. J. Virol. 77: 2369-2376 [Abstract] [Full Text]
Dambrauskas, G., Aves, S. J., Bryant, J. A., Francis, D., Rogers, H. J. (2003). Genes encoding two essential DNA replication activation proteins, Cdc6 and Mcm3, exhibit very different patterns of expression in the tobacco BY-2 cell cycle. J Exp Bot 54: 699-706 [Abstract] [Full Text]
Bermejo, R., Vilaboa, N., Cales, C. (2002). Regulation of CDC6, Geminin, and CDT1 in Human Cells that Undergo Polyploidization. Mol. Biol. Cell 13: 3989-4000 [Abstract] [Full Text]
Blais, A., Monte, D., Pouliot, F., Labrie, C. (2002). Regulation of the Human Cyclin-dependent Kinase Inhibitor p18INK4c by the Transcription Factors E2F1 and Sp1. J. Biol. Chem. 277: 31679-31693 [Abstract] [Full Text]
Yamada, M., Sato, N., Taniyama, C., Ohtani, K., Arai, K.-i., Masai, H. (2002). A 63-Base Pair DNA Segment Containing an Sp1 Site but Not a Canonical E2F Site Can Confer Growth-dependent and E2F-mediated Transcriptional Stimulation of the Human ASK Gene Encoding the Regulatory Subunit for Human Cdc7-related Kinase. J. Biol. Chem. 277: 27668-27681 [Abstract] [Full Text]
Robles, L. D., Frost, A. R., Davila, M., Hutson, A. D., Grizzle, W. E., Chakrabarti, R. (2002). Down-regulation of Cdc6, a Cell Cycle Regulatory Gene, in Prostate Cancer. J. Biol. Chem. 277: 25431-25438 [Abstract] [Full Text]
Fujita, N., Furukawa, Y., Itabashi, N., Okada, K., Saito, T., Ishibashi, S. (2002). Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 283: H204-H212 [Abstract] [Full Text]
Fortunato, E. A., Sanchez, V., Yen, J. Y., Spector, D. H. (2002). Infection of Cells with Human Cytomegalovirus during S Phase Results in a Blockade to Immediate-Early Gene Expression That Can Be Overcome by Inhibition of the Proteasome. J. Virol. 76: 5369-5379 [Abstract] [Full Text]
Blanchard, F., Rusiniak, M. E., Sharma, K., Sun, X., Todorov, I., Castellano, M. M., Gutierrez, C., Baumann, H., Burhans, W. C. (2002). Targeted Destruction of DNA Replication Protein Cdc6 by Cell Death Pathways in Mammals and Yeast. Mol. Biol. Cell 13: 1536-1549 [Abstract] [Full Text]
Cook, J. G., Park, C.-H., Burke, T. W., Leone, G., DeGregori, J., Engel, A., Nevins, J. R. (2002). Analysis of Cdc6 function in the assembly of mammalian prereplication complexes. Proc. Natl. Acad. Sci. USA 10.1073/pnas.032677499v1 [Abstract] [Full Text]
Rialland, M., Sola, F., Santocanale, C. (2002). Essential role of human CDT1 in DNA replication and chromatin licensing. J. Cell Sci. 115: 1435-1440 [Abstract] [Full Text]
Castellano, M. M., del Pozo, J. C., Ramirez-Parra, E., Brown, S., Gutierrez, C. (2001). Expression and Stability of Arabidopsis CDC6 Are Associated with Endoreplication. Plant Cell 13: 2671-2686 [Abstract] [Full Text]
Huang, D., Jokela, M., Tuusa, J., Skog, S., Poikonen, K., Syvaoja, J. E. (2001). E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase {{epsilon}} B-subunit gene POLE2. Nucleic Acids Res 29: 2810-2821 [Abstract] [Full Text]
Chabouté, M.-E., Clément, B., Sekine, M., Philipps, G., Chaubet-Gigot, N. (2000). Cell Cycle Regulation of the Tobacco Ribonucleotide Reductase Small Subunit Gene Is Mediated by E2F-like Elements. Plant Cell 12: 1987-2000 [Abstract] [Full Text]
Petersen, B. O., Wagener, C., Marinoni, F., Kramer, E. R., Melixetian, M., Denchi, E. L., Gieffers, C., Matteucci, C., Peters, J.-M., Helin, K. (2000). Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1. Genes Dev. 14: 2330-2343 [Abstract] [Full Text]
McElroy, A. K., Dwarakanath, R. S., Spector, D. H. (2000). Dysregulation of Cyclin E Gene Expression in Human Cytomegalovirus-Infected Cells Requires Viral Early Gene Expression and Is Associated with Changes in the Rb-Related Protein p130. J. Virol. 74: 4192-4206 [Abstract] [Full Text]
Nishikawa, N. S., Izumi, M., Uchida, H., Yokoi, M., Miyazawa, H., Hanaoka, F. (2000). Cloning and characterization of the 5'-upstream sequence governing the cell cycle-dependent transcription of mouse DNA polymerase {alpha} 68 kDa subunit gene. Nucleic Acids Res 28: 1525-1534 [Abstract] [Full Text]
Takahashi, Y., Rayman, J. B., Dynlacht, B. D. (2000). Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 14: 804-816 [Abstract] [Full Text]
Nicolas, E., Morales, V., Magnaghi-Jaulin, L., Harel-Bellan, A., Richard-Foy, H., Trouche, D. (2000). RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein. J. Biol. Chem. 275: 9797-9804 [Abstract] [Full Text]
Fedele, M., Benvenuto, G., Pero, R., Majello, B., Battista, S., Lembo, F., Vollono, E., Day, P. M., Santoro, M., Lania, L., Bruni, C. B., Fusco, A., Chiariotti, L. (2000). A Novel Member of the BTB/POZ Family, PATZ, Associates with the RNF4 RING Finger Protein and Acts as a Transcriptional Repressor. J. Biol. Chem. 275: 7894-7901 [Abstract] [Full Text]
Schaley, J., O'Connor, R. J., Taylor, L. J., Bar-Sagi, D., Hearing, P. (2000). Induction of the Cellular E2F-1 Promoter by the Adenovirus E4-6/7 Protein. J. Virol. 74: 2084-2093 [Abstract] [Full Text]
Arata, Y., Fujita, M., Ohtani, K., Kijima, S., Kato, J.-y. (2000). Cdk2-dependent and -independent Pathways in E2F-mediated S Phase Induction. J. Biol. Chem. 275: 6337-6345 [Abstract] [Full Text]
Yan, Z., Fedorov, S. A., Mumby, M. C., Williams, R. S. (2000). PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells. Mol. Cell. Biol. 20: 1021-1029 [Abstract] [Full Text]
Coverley, D, Pelizon, C, Trewick, S, Laskey, R. (2000). Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process. J. Cell Sci. 113: 1929-1938 [Abstract]
Tommasi, S., Pfeifer, G. P. (1999). In Vivo Structure of Two Divergent Promoters at the Human PCNA Locus. SYNTHESIS OF ANTISENSE RNA AND S PHASE-DEPENDENT BINDING OF E2F COMPLEXES IN INTRON 1. J. Biol. Chem. 274: 27829-27838 [Abstract] [Full Text]
Vigo, E., Muller, H., Prosperini, E., Hateboer, G., Cartwright, P., Moroni, M. C., Helin, K. (1999). CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F-Induced S Phase. Mol. Cell. Biol. 19: 6379-6395 [Abstract] [Full Text]
Herbig, U., Marlar, C. A., Fanning, E. (1999). The Cdc6 Nucleotide-Binding Site Regulates Its Activity in DNA Replication in Human Cells. Mol. Biol. Cell 10: 2631-2645 [Abstract] [Full Text]
Kumagai, H., Sato, N., Yamada, M., Mahony, D., Seghezzi, W., Lees, E., Arai, K.-I., Masai, H. (1999). A Novel Growth- and Cell Cycle-Regulated Protein, ASK, Activates Human Cdc7-Related Kinase and Is Essential for G1/S Transition in Mammalian Cells. Mol. Cell. Biol. 19: 5083-5095 [Abstract] [Full Text]
Sanchez, M, Calzada, A, Bueno, A (1999). Functionally homologous DNA replication genes in fission and budding yeast. J. Cell Sci. 112: 2381-2390 [Abstract]
Wu, F., Lee, A. S. (2001). YY1 as a Regulator of Replication-dependent Hamster Histone H3.2 Promoter and an Interactive Partner of AP-2. J. Biol. Chem. 276: 28-34 [Abstract] [Full Text]
Korner, K., Jerome, V., Schmidt, T., Muller, R. (2001). Cell Cycle Regulation of the Murine cdc25B Promoter. ESSENTIAL ROLE FOR NUCLEAR FACTOR-Y AND A PROXIMAL REPRESSOR ELEMENT. J. Biol. Chem. 276: 9662-9669 [Abstract] [Full Text]
Kondo, T., Higashi, H., Nishizawa, H., Ishikawa, S., Ashizawa, S., Yamada, M., Makita, Z., Koike, T., Hatakeyama, M. (2001). Involvement of pRB-related p107 Protein in the Inhibition of S Phase Progression in Response to Genotoxic Stress. J. Biol. Chem. 276: 17559-17567 [Abstract] [Full Text]
Nishitani, H., Taraviras, S., Lygerou, Z., Nishimoto, T. (2001). The Human Licensing Factor for DNA Replication Cdt1 Accumulates in G1 and Is Destabilized after Initiation of S-phase. J. Biol. Chem. 276: 44905-44911 [Abstract] [Full Text]
Alexandrow, M. G., Ritzi, M., Pemov, A., Hamlin, J. L. (2002). A Potential Role for Mini-chromosome Maintenance (MCM) Proteins in Initiation at the Dihydrofolate Reductase Replication Origin. J. Biol. Chem. 277: 2702-2708 [Abstract] [Full Text]
Cook, J. G., Park, C.-H., Burke, T. W., Leone, G., DeGregori, J., Engel, A., Nevins, J. R. (2002). Analysis of Cdc6 function in the assembly of mammalian prereplication complexes. Proc. Natl. Acad. Sci. USA 99: 1347-1352 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals