Protein-coding gene in humans
Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene .[ 5] [ 6]
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.[ 7]
Interactions CDC6 has been shown to interact with ORC1L ,[ 6] [ 8] ORC2L ,[ 8] [ 9] Cyclin A2 ,[ 6] [ 10] PPP2R3B ,[ 11] MCM3 ,[ 9] [ 12] PPP2R3A ,[ 13] MCM7 [ 8] [ 12] PSKH1 .[ 10]
See also Cdc6 , the family of orthologs in eukaryotes
References
^ a b c GRCh38: Ensembl release 89: ENSG00000094804 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017499 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Williams RS, Shohet RV, Stillman B (February 1997). "A human protein related to yeast Cdc6p" . Proc Natl Acad Sci U S A . 94 (1): 142– 7. Bibcode :1997PNAS...94..142S . doi :10.1073/pnas.94.1.142 PMC 19260 PMID 8990175 . ^ a b c Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A (May 1998). "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. doi :10.1128/mcb.18.5.2758 . PMC 110655 PMID 9566895 . ^ "Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae)" .^ a b c 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). England: 111– 28. doi :10.1016/S0022-2836(03)00079-2 . ISSN 0022-2836 . PMID 12614612 . ^ a b 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). UNITED STATES: 8602– 12. doi :10.1128/MCB.20.22.8602-8612.2000 . ISSN 0270-7306 . PMC 102165 PMID 11046155 . ^ a b 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). ENGLAND: 396– 410. doi :10.1093/emboj/18.2.396 . ISSN 0261-4189 . PMC 1171134 PMID 9889196 . ^ 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). UNITED STATES: 1021– 9. doi :10.1128/MCB.20.3.1021-1029.2000 . ISSN 0270-7306 . PMC 85219 PMID 10629059 . ^ a b 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). UNITED STATES: 25927– 32. doi :10.1074/jbc.274.36.25927 ISSN 0021-9258 . PMID 10464337 . ^ 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). United States: 16104– 14. doi :10.1074/jbc.M710313200 ISSN 0021-9258 . PMC 2414307 PMID 18397887 .
Further reading
Yan Z, DeGregori J, Shohet R, et al. (1998). "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. Bibcode :1998PNAS...95.3603Y . doi :10.1073/pnas.95.7.3603 PMC 19882 PMID 9520412 . Hateboer G, Wobst A, Petersen BO, et al. (1998). "Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F" . Mol. Cell. Biol . 18 (11): 6679– 97. doi :10.1128/mcb.18.11.6679 . PMC 109252 PMID 9774682 . Ohtani K, Tsujimoto A, Ikeda M, Nakamura M (1998). "Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F" . Oncogene . 17 (14): 1777– 85. doi :10.1038/sj.onc.1202105 PMID 9778043 . Stoeber K, Mills AD, Kubota Y, et al. (1999). "Cdc6 protein causes premature entry into S phase in a mammalian cell-free system" . EMBO J . 17 (24): 7219– 29. doi :10.1093/emboj/17.24.7219 . PMC 1171068 PMID 9857179 . Petersen BO, Lukas J, Sørensen CS, et al. (1999). "Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization" . EMBO J . 18 (2): 396– 410. doi :10.1093/emboj/18.2.396 . PMC 1171134 PMID 9889196 . van Hannen EJ, Zwart G, van Agterveld MP, et al. (1999). "Changes in Bacterial and Eukaryotic Community Structure after Mass Lysis of Filamentous Cyanobacteria Associated with Viruses" . Appl. Environ. Microbiol . 65 (2): 795– 801. Bibcode :1999ApEnM..65..795V . doi :10.1128/AEM.65.2.795-801.1999 . PMC 91097 PMID 9925618 . Takei Y, Yamamoto K, Tsujimoto G (1999). "Identification of the sequence responsible for the nuclear localization of human Cdc6" . FEBS Lett . 447 (2– 3): 292– 6. doi :10.1016/S0014-5793(99)00306-3 PMID 10214964 . S2CID 39852055 . Jiang W, Wells NJ, Hunter T (1999). "Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6" . Proc. Natl. Acad. Sci. U.S.A . 96 (11): 6193– 8. Bibcode :1999PNAS...96.6193J . doi :10.1073/pnas.96.11.6193 PMC 26858 PMID 10339564 . Fujita M, Yamada C, Goto H, et al. (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. doi :10.1074/jbc.274.36.25927 PMID 10464337 . Yan Z, Fedorov SA, Mumby MC, Williams RS (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. doi :10.1128/MCB.20.3.1021-1029.2000 . PMC 85219 PMID 10629059 . Takahashi Y, Rayman JB, Dynlacht BD (2000). "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. doi :10.1101/gad.14.7.804 . PMC 316494 PMID 10766737 . Takayama M, Taira T, Iguchi-Ariga SM, Ariga H (2000). "CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex" . FEBS Lett . 477 (1– 2): 43– 8. doi :10.1016/S0014-5793(00)01756-7 PMID 10899308 . S2CID 12965556 . Petersen BO, Wagener C, Marinoni F, et al. (2000). "Cell cycle– and cell growth–regulated proteolysis of mammalian CDC6 is dependent on APC–CDH1" . Genes Dev . 14 (18): 2330– 43. doi :10.1101/gad.832500 . PMC 316932 PMID 10995389 . Méndez J, Stillman B (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. doi :10.1128/MCB.20.22.8602-8612.2000 . PMC 102165 PMID 11046155 . Delmolino LM, Saha P, Dutta A (2001). "Multiple mechanisms regulate subcellular localization of human CDC6" . J. Biol. Chem . 276 (29): 26947– 54. doi :10.1074/jbc.M101870200 PMID 11346650 . Fujita M, Ishimi Y, Nakamura H, et al. (2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells" . J. Biol. Chem . 277 (12): 10354– 61. doi :10.1074/jbc.M111398200 PMID 11779870 . Biermann E, Baack M, Kreitz S, Knippers R (2002). "Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle" . Eur. J. Biochem . 269 (3): 1040– 6. doi :10.1046/j.0014-2956.2001.02746.x PMID 11846807 . Robles LD, Frost AR, Davila M, et al. (2002). "Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer" . J. Biol. Chem . 277 (28): 25431– 8. doi :10.1074/jbc.M201199200 PMID 12006585 .
External links
