CDC6 explained
Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.[1] [2]
The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in the cell nucleus during cell cycle phase G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during the cell cycle is regulated through its phosphorylation by cyclin-dependent kinases. Transcription of this protein was reported to be regulated in response to mitogenic signals through a transcriptional control mechanism involving E2F proteins.[3]
Interactions
CDC6 has been shown to interact with ORC1L,[4] ORC2L,[4] [5] Cyclin A2,[2] [6] PPP2R3B,[7] MCM3,[5] [8] PPP2R3A,[9] MCM7[4] [8] and PSKH1.[6]
See also
- Cdc6, the family of orthologs in eukaryotes
Further reading
- Yan Z, DeGregori J, Shohet R . Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells . Proc. Natl. Acad. Sci. U.S.A. . 95 . 7 . 3603–8 . 1998 . 9520412 . 19882 . 10.1073/pnas.95.7.3603 . etal. 1998PNAS...95.3603Y. free .
- Hateboer G, Wobst A, Petersen BO . Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F . Mol. Cell. Biol. . 18 . 11 . 6679–97 . 1998 . 9774682 . 109252 . 10.1128/mcb.18.11.6679. etal.
- Ohtani K, Tsujimoto A, Ikeda M, Nakamura M . Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F . Oncogene . 17 . 14 . 1777–85 . 1998 . 9778043 . 10.1038/sj.onc.1202105 . free .
- Stoeber K, Mills AD, Kubota Y . Cdc6 protein causes premature entry into S phase in a mammalian cell-free system . EMBO J. . 17 . 24 . 7219–29 . 1999 . 9857179 . 1171068 . 10.1093/emboj/17.24.7219 . etal.
- Petersen BO, Lukas J, Sørensen CS . Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization . EMBO J. . 18 . 2 . 396–410 . 1999 . 9889196 . 1171134 . 10.1093/emboj/18.2.396 . etal.
- van Hannen EJ, Zwart G, van Agterveld MP . Changes in Bacterial and Eukaryotic Community Structure after Mass Lysis of Filamentous Cyanobacteria Associated with Viruses . Appl. Environ. Microbiol. . 65 . 2 . 795–801 . 1999 . 9925618 . 91097 . 10.1128/AEM.65.2.795-801.1999. 1999ApEnM..65..795V . etal.
- Takei Y, Yamamoto K, Tsujimoto G . Identification of the sequence responsible for the nuclear localization of human Cdc6 . FEBS Lett. . 447 . 2–3 . 292–6 . 1999 . 10214964 . 10.1016/S0014-5793(99)00306-3 . 39852055 . free .
- Jiang W, Wells NJ, Hunter T . Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6 . Proc. Natl. Acad. Sci. U.S.A. . 96 . 11 . 6193–8 . 1999 . 10339564 . 26858 . 10.1073/pnas.96.11.6193 . 1999PNAS...96.6193J . free .
- Fujita M, Yamada C, Goto H . Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation . J. Biol. Chem. . 274 . 36 . 25927–32 . 1999 . 10464337 . 10.1074/jbc.274.36.25927 . etal. free .
- Yan Z, Fedorov SA, Mumby MC, Williams RS . PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells . Mol. Cell. Biol. . 20 . 3 . 1021–9 . 2000 . 10629059 . 85219 . 10.1128/MCB.20.3.1021-1029.2000 .
- Takahashi Y, Rayman JB, Dynlacht BD . Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression . Genes Dev. . 14 . 7 . 804–16 . 2000 . 10766737 . 316494 . 10.1101/gad.14.7.804 .
- Takayama M, Taira T, Iguchi-Ariga SM, Ariga H . CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex . FEBS Lett. . 477 . 1–2 . 43–8 . 2000 . 10899308 . 10.1016/S0014-5793(00)01756-7 . 12965556 . free .
- Petersen BO, Wagener C, Marinoni F . Cell cycle– and cell growth–regulated proteolysis of mammalian CDC6 is dependent on APC–CDH1 . Genes Dev. . 14 . 18 . 2330–43 . 2000 . 10995389 . 316932 . 10.1101/gad.832500 . etal.
- Méndez J, Stillman B . Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis . Mol. Cell. Biol. . 20 . 22 . 8602–12 . 2000 . 11046155 . 102165 . 10.1128/MCB.20.22.8602-8612.2000 .
- Delmolino LM, Saha P, Dutta A . Multiple mechanisms regulate subcellular localization of human CDC6 . J. Biol. Chem. . 276 . 29 . 26947–54 . 2001 . 11346650 . 10.1074/jbc.M101870200 . free .
- Fujita M, Ishimi Y, Nakamura H . Nuclear organization of DNA replication initiation proteins in mammalian cells . J. Biol. Chem. . 277 . 12 . 10354–61 . 2002 . 11779870 . 10.1074/jbc.M111398200 . etal. free .
- Biermann E, Baack M, Kreitz S, Knippers R . Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle . Eur. J. Biochem. . 269 . 3 . 1040–6 . 2002 . 11846807 . 10.1046/j.0014-2956.2001.02746.x . free .
- Robles LD, Frost AR, Davila M . Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer . J. Biol. Chem. . 277 . 28 . 25431–8 . 2002 . 12006585 . 10.1074/jbc.M201199200 . etal. free .
Notes and References
- Williams RS, Shohet RV, Stillman B . A human protein related to yeast Cdc6p . Proc Natl Acad Sci U S A . 94 . 1 . 142–7 . February 1997 . 8990175 . 19260 . 10.1073/pnas.94.1.142 . 1997PNAS...94..142S . free .
- Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A . Human CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase . Mol Cell Biol . 18 . 5 . 2758–67 . May 1998 . 9566895 . 110655 . 10.1128/mcb.18.5.2758.
- Web site: Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae).
- 10.1016/S0022-2836(03)00079-2 . Kneissl . Margot . Pütter Vera . Szalay Aladar A . Grummt Friedrich . March 2003 . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . J. Mol. Biol. . 327 . 1 . 111–28 . England. 0022-2836. 12614612 .
- 10.1128/MCB.20.22.8602-8612.2000 . Méndez . J . Stillman B . November 2000 . Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis . Mol. Cell. Biol. . 20 . 22 . 8602–12 . UNITED STATES. 0270-7306. 11046155 . 102165 .
- Petersen . B O . Lukas J. Sørensen C S. Bartek J. Helin K . January 1999 . Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization . EMBO J. . 18 . 2 . 396–410 . ENGLAND. 0261-4189. 9889196 . 1171134 . 10.1093/emboj/18.2.396 .
- 10.1128/MCB.20.3.1021-1029.2000 . Yan . Z . Fedorov S A. Mumby M C. Williams R S . February 2000 . PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells . Mol. Cell. Biol. . 20 . 3 . 1021–9 . UNITED STATES. 0270-7306. 10629059 . 85219 .
- 10.1074/jbc.274.36.25927 . Fujita . M . Yamada C. Goto H. Yokoyama N. Kuzushima K. Inagaki M. Tsurumi T . September 1999 . Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation . J. Biol. Chem. . 274 . 36 . 25927–32 . UNITED STATES. 0021-9258. 10464337 . free .
- Davis . Anthony J . Yan Zhen . Martinez Bobbie . Mumby Marc C . June 2008 . Protein Phosphatase 2A Is Targeted to Cell Division Control Protein 6 by a Calcium-binding Regulatory Subunit . J. Biol. Chem. . 283 . 23 . 16104–14 . United States. 0021-9258. 18397887 . 2414307 . 10.1074/jbc.M710313200 . free .