Biology:CDC6
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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,[2][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
References
- ↑ "A human protein related to yeast Cdc6p". Proc Natl Acad Sci U S A 94 (1): 142–7. February 1997. doi:10.1073/pnas.94.1.142. PMID 8990175. Bibcode: 1997PNAS...94..142S.
- ↑ 2.0 2.1 2.2 "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. doi:10.1128/mcb.18.5.2758. PMID 9566895.
- ↑ "Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=990.
- ↑ 4.0 4.1 4.2 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. (England) 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. ISSN 0022-2836. PMID 12614612.
- ↑ 5.0 5.1 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. (UNITED STATES) 20 (22): 8602–12. doi:10.1128/MCB.20.22.8602-8612.2000. ISSN 0270-7306. PMID 11046155.
- ↑ 6.0 6.1 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. (ENGLAND) 18 (2): 396–410. doi:10.1093/emboj/18.2.396. ISSN 0261-4189. 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. (UNITED STATES) 20 (3): 1021–9. doi:10.1128/MCB.20.3.1021-1029.2000. ISSN 0270-7306. PMID 10629059.
- ↑ 8.0 8.1 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. (UNITED STATES) 274 (36): 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. (United States) 283 (23): 16104–14. doi:10.1074/jbc.M710313200. ISSN 0021-9258. PMID 18397887.
Further reading
- "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. doi:10.1073/pnas.95.7.3603. PMID 9520412. Bibcode: 1998PNAS...95.3603Y.
- "Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F". Mol. Cell. Biol. 18 (11): 6679–97. 1998. doi:10.1128/mcb.18.11.6679. PMID 9774682.
- "Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F". Oncogene 17 (14): 1777–85. 1998. doi:10.1038/sj.onc.1202105. PMID 9778043.
- "Cdc6 protein causes premature entry into S phase in a mammalian cell-free system". EMBO J. 17 (24): 7219–29. 1999. doi:10.1093/emboj/17.24.7219. PMID 9857179.
- "Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization". EMBO J. 18 (2): 396–410. 1999. doi:10.1093/emboj/18.2.396. PMID 9889196.
- "Changes in Bacterial and Eukaryotic Community Structure after Mass Lysis of Filamentous Cyanobacteria Associated with Viruses". Appl. Environ. Microbiol. 65 (2): 795–801. 1999. doi:10.1128/AEM.65.2.795-801.1999. PMID 9925618. Bibcode: 1999ApEnM..65..795V.
- "Identification of the sequence responsible for the nuclear localization of human Cdc6". FEBS Lett. 447 (2–3): 292–6. 1999. doi:10.1016/S0014-5793(99)00306-3. PMID 10214964.
- "Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6". Proc. Natl. Acad. Sci. U.S.A. 96 (11): 6193–8. 1999. doi:10.1073/pnas.96.11.6193. PMID 10339564. Bibcode: 1999PNAS...96.6193J.
- "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. doi:10.1074/jbc.274.36.25927. PMID 10464337.
- "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. doi:10.1128/MCB.20.3.1021-1029.2000. PMID 10629059.
- "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. doi:10.1101/gad.14.7.804. PMID 10766737.
- "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. doi:10.1016/S0014-5793(00)01756-7. PMID 10899308.
- "Cell cycle– and cell growth–regulated proteolysis of mammalian CDC6 is dependent on APC–CDH1". Genes Dev. 14 (18): 2330–43. 2000. doi:10.1101/gad.832500. PMID 10995389.
- "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. doi:10.1128/MCB.20.22.8602-8612.2000. PMID 11046155.
- "Multiple mechanisms regulate subcellular localization of human CDC6". J. Biol. Chem. 276 (29): 26947–54. 2001. doi:10.1074/jbc.M101870200. PMID 11346650.
- "Nuclear organization of DNA replication initiation proteins in mammalian cells". J. Biol. Chem. 277 (12): 10354–61. 2002. doi:10.1074/jbc.M111398200. PMID 11779870.
- "Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle". Eur. J. Biochem. 269 (3): 1040–6. 2002. doi:10.1046/j.0014-2956.2001.02746.x. PMID 11846807.
- "Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer". J. Biol. Chem. 277 (28): 25431–8. 2002. doi:10.1074/jbc.M201199200. PMID 12006585.
External links
- Human CDC6 genome location and CDC6 gene details page in the UCSC Genome Browser.
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