Integrated computational model of cell cycle and checkpoint reveals different essential roles of Aurora-A and Plk1 in mitotic entry
Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects...
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| Published in | Molecular bioSystems Vol. 7; no. 1; pp. 169 - 179 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
2011
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| Subjects | |
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| Abstract | Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects are how mitotic entry is controlled by its upstream regulators Aurora-A and Plk1, and how mitotic entry is coordinated with other biological events, especially G2/M checkpoint. In this context, we reconstructed a comprehensive computational model that integrates the mitotic entry network and the G2/M checkpoint system. Computational simulation of this model and subsequent experimental verification revealed that Aurora-A and Plk1 are redundant to the activation of cyclin B/Cdk1 during normal mitotic entry, but become especially important for cyclin B/Cdk1 activation during G2/M checkpoint recovery. Further analysis indicated that, in response to DNA damage, Chk1-mediated network rewiring makes cyclin B/Cdk1 more sensitive to the down-regulation of Aurora-A and Plk1. In addition, we demonstrated that concurrently targeting Aurora-A and Plk1 during G2/M checkpoint recovery achieves a synergistic effect, which suggests the combinational use of Aurora-A and Plk1 inhibitors after chemotherapy or radiotherapy. Thus, the results presented here provide novel insights into the regulation mechanism of mitotic entry and have potential value in cancer therapy. |
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| AbstractList | Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects are how mitotic entry is controlled by its upstream regulators Aurora-A and Plk1, and how mitotic entry is coordinated with other biological events, especially G2/M checkpoint. In this context, we reconstructed a comprehensive computational model that integrates the mitotic entry network and the G2/M checkpoint system. Computational simulation of this model and subsequent experimental verification revealed that Aurora-A and Plk1 are redundant to the activation of cyclin B/Cdk1 during normal mitotic entry, but become especially important for cyclin B/Cdk1 activation during G2/M checkpoint recovery. Further analysis indicated that, in response to DNA damage, Chk1-mediated network rewiring makes cyclin B/Cdk1 more sensitive to the down-regulation of Aurora-A and Plk1. In addition, we demonstrated that concurrently targeting Aurora-A and Plk1 during G2/M checkpoint recovery achieves a synergistic effect, which suggests the combinational use of Aurora-A and Plk1 inhibitors after chemotherapy or radiotherapy. Thus, the results presented here provide novel insights into the regulation mechanism of mitotic entry and have potential value in cancer therapy. Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects are how mitotic entry is controlled by its upstream regulators Aurora-A and Plk1, and how mitotic entry is coordinated with other biological events, especially G2/M checkpoint. In this context, we reconstructed a comprehensive computational model that integrates the mitotic entry network and the G2/M checkpoint system. Computational simulation of this model and subsequent experimental verification revealed that Aurora-A and Plk1 are redundant to the activation of cyclin B/Cdk1 during normal mitotic entry, but become especially important for cyclin B/Cdk1 activation during G2/M checkpoint recovery. Further analysis indicated that, in response to DNA damage, Chk1-mediated network rewiring makes cyclin B/Cdk1 more sensitive to the down-regulation of Aurora-A and Plk1. In addition, we demonstrated that concurrently targeting Aurora-A and Plk1 during G2/M checkpoint recovery achieves a synergistic effect, which suggests the combinational use of Aurora-A and Plk1 inhibitors after chemotherapy or radiotherapy. Thus, the results presented here provide novel insights into the regulation mechanism of mitotic entry and have potential value in cancer therapy.Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects are how mitotic entry is controlled by its upstream regulators Aurora-A and Plk1, and how mitotic entry is coordinated with other biological events, especially G2/M checkpoint. In this context, we reconstructed a comprehensive computational model that integrates the mitotic entry network and the G2/M checkpoint system. Computational simulation of this model and subsequent experimental verification revealed that Aurora-A and Plk1 are redundant to the activation of cyclin B/Cdk1 during normal mitotic entry, but become especially important for cyclin B/Cdk1 activation during G2/M checkpoint recovery. Further analysis indicated that, in response to DNA damage, Chk1-mediated network rewiring makes cyclin B/Cdk1 more sensitive to the down-regulation of Aurora-A and Plk1. In addition, we demonstrated that concurrently targeting Aurora-A and Plk1 during G2/M checkpoint recovery achieves a synergistic effect, which suggests the combinational use of Aurora-A and Plk1 inhibitors after chemotherapy or radiotherapy. Thus, the results presented here provide novel insights into the regulation mechanism of mitotic entry and have potential value in cancer therapy. |
| Author | Luo, Shi-Dong Yang, Sheng-Yong Wei, Yu-Quan Zou, Jun |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20978655$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1145/1089014.1089020 10.1038/ncb954 10.1038/msb4100126 10.1038/nchembio817 10.1038/sj.embor.embor887 10.1038/nrd2683 10.1016/j.ceb.2008.10.005 10.1016/j.cub.2006.12.046 10.1038/nrc2248 10.1038/ncb0707-724 10.1186/1752-0509-2-47 10.1016/j.cell.2005.06.016 10.1038/nrd2381 10.1038/nrm2351 10.1242/jcs.106.4.1153 10.1016/j.ceb.2009.01.018 10.1111/j.1744-7348.1939.tb06990.x 10.1073/pnas.0608798104 10.1038/nrc1841 10.1038/nrm2510 10.1111/j.1742-4658.2008.06844.x 10.1038/nrc2169 10.1111/j.1747-0285.2008.00663.x 10.1038/nbt1330 10.1038/msb.2008.80 10.1016/j.cub.2006.08.026 10.1038/nrm2653 10.1083/jcb.200812045 10.1038/nrd2907 10.1016/j.ceb.2007.11.008 10.1038/nbt.1549 10.1016/j.bmcl.2008.08.033 10.1007/PL00011391 10.1126/science.1156951 10.1126/scisignal.2000352 10.1038/nrg2102 10.1186/1752-0509-4-11 10.1016/j.apnum.2007.09.001 10.1073/pnas.0500410102 10.1038/nrc1502 10.1038/nrd2195 10.1126/science.1073096 10.1038/msb.2008.74 10.1039/b907562n 10.1083/jcb.200712027 10.1021/bi0009643 10.1038/nrc2787 10.1126/science.1157425 10.1038/nm1003 10.1158/0008-5472.CAN-05-1054 10.1093/nar/28.1.27 10.1038/msb.2009.4 10.1039/B907863K 10.1016/j.molcel.2006.06.013 10.1021/jm8012129 10.1038/nrc2602 10.1016/j.cell.2009.02.024 10.1093/nar/gki072 10.1016/j.molcel.2006.06.016 10.1128/MCB.15.1.345 10.1038/nature07185 10.1093/bib/bbp005 |
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| References | Novák (C0MB00004C-(cit3)/*[position()=1]) 1993; 106 Pomerening (C0MB00004C-(cit5)/*[position()=1]) 2003; 5 Haberichter (C0MB00004C-(cit56)/*[position()=1]) 2007; 3 Malumbres (C0MB00004C-(cit1)/*[position()=1]) 2009; 9 Taylor (C0MB00004C-(cit16)/*[position()=1]) 2008; 20 Lindqvist (C0MB00004C-(cit2)/*[position()=1]) 2009; 185 Wang (C0MB00004C-(cit22)/*[position()=1]) 2008; 18 Schlier (C0MB00004C-(cit47)/*[position()=1]) 2008; 58 Watanabe (C0MB00004C-(cit33)/*[position()=1]) 2005; 102 Chen (C0MB00004C-(cit45)/*[position()=1]) 2008; 5 Boutros (C0MB00004C-(cit14)/*[position()=1]) 2007; 7 Csikasz-Nagy (C0MB00004C-(cit17)/*[position()=1]) 2009; 10 Donzelli (C0MB00004C-(cit13)/*[position()=1]) 2003; 4 Banga (C0MB00004C-(cit41)/*[position()=1]) 2008; 2 Pollard (C0MB00004C-(cit23)/*[position()=1]) 2009; 52 Lapenna (C0MB00004C-(cit24)/*[position()=1]) 2009; 8 Manfredi (C0MB00004C-(cit32)/*[position()=1]) 2007; 104 Keen (C0MB00004C-(cit51)/*[position()=1]) 2004; 4 Lobrich (C0MB00004C-(cit12)/*[position()=1]) 2007; 7 Strebhardt (C0MB00004C-(cit20)/*[position()=1]) 2006; 6 Kanehisa (C0MB00004C-(cit28)/*[position()=1]) 2000; 28 Vugt (C0MB00004C-(cit37)/*[position()=1]) 2005; 65 Byrd (C0MB00004C-(cit48)/*[position()=1]) 2000; 89 Harrington (C0MB00004C-(cit55)/*[position()=1]) 2004; 10 Bliss (C0MB00004C-(cit54)/*[position()=1]) 1939; 26 Macůrek (C0MB00004C-(cit10)/*[position()=1]) 2008; 455 Hlavacek (C0MB00004C-(cit39)/*[position()=1]) 2008; 5 Seki (C0MB00004C-(cit34)/*[position()=1]) 2008; 181 Branzei (C0MB00004C-(cit35)/*[position()=1]) 2008; 9 Ashyraliyev (C0MB00004C-(cit40)/*[position()=1]) 2009; 276 Tsai (C0MB00004C-(cit58)/*[position()=1]) 2008; 321 Mailand (C0MB00004C-(cit38)/*[position()=1]) 2006; 23 Mamely (C0MB00004C-(cit15)/*[position()=1]) 2006; 16 Schoeberl (C0MB00004C-(cit27)/*[position()=1]) 2009; 2 Desai (C0MB00004C-(cit50)/*[position()=1]) 1995; 15 Joshi-Tope (C0MB00004C-(cit29)/*[position()=1]) 2004; 33 Jia (C0MB00004C-(cit25)/*[position()=1]) 2009; 8 Pomerening (C0MB00004C-(cit6)/*[position()=1]) 2005; 122 Takaki (C0MB00004C-(cit7)/*[position()=1]) 2008; 20 Kitano (C0MB00004C-(cit52)/*[position()=1]) 2007; 6 Arooz (C0MB00004C-(cit31)/*[position()=1]) 2000; 39 Knight (C0MB00004C-(cit62)/*[position()=1]) 2010; 10 Weinstein (C0MB00004C-(cit60)/*[position()=1]) 2002; 297 Vera (C0MB00004C-(cit19)/*[position()=1]) 2010; 6 Alon (C0MB00004C-(cit59)/*[position()=1]) 2007; 8 Peschiaroli (C0MB00004C-(cit43)/*[position()=1]) 2006; 23 Kuepfer (C0MB00004C-(cit44)/*[position()=1]) 2007; 25 Vader (C0MB00004C-(cit11)/*[position()=1]) 2008; 1786 Archambault (C0MB00004C-(cit8)/*[position()=1]) 2009; 10 Fitzgerald (C0MB00004C-(cit26)/*[position()=1]) 2006; 2 Deng (C0MB00004C-(cit21)/*[position()=1]) 2008; 71 Lenart (C0MB00004C-(cit42)/*[position()=1]) 2007; 17 Luo (C0MB00004C-(cit61)/*[position()=1]) 2009; 136 Novák (C0MB00004C-(cit4)/*[position()=1]) 2007; 9 Balsa-Canto (C0MB00004C-(cit49)/*[position()=1]) 2010; 4 Lehár (C0MB00004C-(cit53)/*[position()=1]) 2009; 27 Seki (C0MB00004C-(cit9)/*[position()=1]) 2008; 320 Araujo (C0MB00004C-(cit18)/*[position()=1]) 2007; 6 Faure (C0MB00004C-(cit57)/*[position()=1]) 2009; 5 Wang (C0MB00004C-(cit46)/*[position()=1]) 2009; 5 Hochegger (C0MB00004C-(cit30)/*[position()=1]) 2008; 9 Hindmarsh (C0MB00004C-(cit63)/*[position()=1]) 2005; 31 Reinhardt (C0MB00004C-(cit36)/*[position()=1]) 2009; 21 |
| References_xml | – volume: 31 start-page: 363 year: 2005 ident: C0MB00004C-(cit63)/*[position()=1] publication-title: Assoc. Comput. Mach., Trans. Math. Software doi: 10.1145/1089014.1089020 – volume: 5 start-page: 346 year: 2003 ident: C0MB00004C-(cit5)/*[position()=1] publication-title: Nat. Cell Biol. doi: 10.1038/ncb954 – volume: 3 start-page: 84 year: 2007 ident: C0MB00004C-(cit56)/*[position()=1] publication-title: Mol. Syst. Biol. doi: 10.1038/msb4100126 – volume: 2 start-page: 458 year: 2006 ident: C0MB00004C-(cit26)/*[position()=1] publication-title: Nat. Chem. Biol. doi: 10.1038/nchembio817 – volume: 4 start-page: 671 year: 2003 ident: C0MB00004C-(cit13)/*[position()=1] publication-title: EMBO Rep. doi: 10.1038/sj.embor.embor887 – volume: 8 start-page: 111 year: 2009 ident: C0MB00004C-(cit25)/*[position()=1] publication-title: Nat. Rev. Drug Discovery doi: 10.1038/nrd2683 – volume: 20 start-page: 650 year: 2008 ident: C0MB00004C-(cit7)/*[position()=1] publication-title: Curr. Opin. Cell Biol. doi: 10.1016/j.ceb.2008.10.005 – volume: 17 start-page: 304 year: 2007 ident: C0MB00004C-(cit42)/*[position()=1] publication-title: Curr. Biol. doi: 10.1016/j.cub.2006.12.046 – volume: 7 start-page: 861 year: 2007 ident: C0MB00004C-(cit12)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2248 – volume: 9 start-page: 724 year: 2007 ident: C0MB00004C-(cit4)/*[position()=1] publication-title: Nat. Cell Biol. doi: 10.1038/ncb0707-724 – volume: 2 start-page: 47 year: 2008 ident: C0MB00004C-(cit41)/*[position()=1] publication-title: BMC Syst. Biol. doi: 10.1186/1752-0509-2-47 – volume: 122 start-page: 565 year: 2005 ident: C0MB00004C-(cit6)/*[position()=1] publication-title: Cell doi: 10.1016/j.cell.2005.06.016 – volume: 6 start-page: 871 year: 2007 ident: C0MB00004C-(cit18)/*[position()=1] publication-title: Nat. Rev. Drug Discovery doi: 10.1038/nrd2381 – volume: 9 start-page: 297 year: 2008 ident: C0MB00004C-(cit35)/*[position()=1] publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2351 – volume: 106 start-page: 1153 year: 1993 ident: C0MB00004C-(cit3)/*[position()=1] publication-title: J. Cell Sci. doi: 10.1242/jcs.106.4.1153 – volume: 21 start-page: 245 year: 2009 ident: C0MB00004C-(cit36)/*[position()=1] publication-title: Curr. Opin. Cell Biol. doi: 10.1016/j.ceb.2009.01.018 – volume: 26 start-page: 585 year: 1939 ident: C0MB00004C-(cit54)/*[position()=1] publication-title: Ann. Appl. Biol. doi: 10.1111/j.1744-7348.1939.tb06990.x – volume: 104 start-page: 4106 year: 2007 ident: C0MB00004C-(cit32)/*[position()=1] publication-title: Proc. Natl. Acad. Sci. U. S. A. doi: 10.1073/pnas.0608798104 – volume: 1786 start-page: 60 year: 2008 ident: C0MB00004C-(cit11)/*[position()=1] publication-title: Biochim. Biophys. Acta – volume: 6 start-page: 321 year: 2006 ident: C0MB00004C-(cit20)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc1841 – volume: 9 start-page: 910 year: 2008 ident: C0MB00004C-(cit30)/*[position()=1] publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2510 – volume: 276 start-page: 886 year: 2009 ident: C0MB00004C-(cit40)/*[position()=1] publication-title: FEBS J. doi: 10.1111/j.1742-4658.2008.06844.x – volume: 7 start-page: 495 year: 2007 ident: C0MB00004C-(cit14)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2169 – volume: 71 start-page: 533 year: 2008 ident: C0MB00004C-(cit21)/*[position()=1] publication-title: Chem. Biol. Drug Des. doi: 10.1111/j.1747-0285.2008.00663.x – volume: 25 start-page: 1001 year: 2007 ident: C0MB00004C-(cit44)/*[position()=1] publication-title: Nat. Biotechnol. doi: 10.1038/nbt1330 – volume: 5 start-page: 240 year: 2008 ident: C0MB00004C-(cit39)/*[position()=1] publication-title: Mol. Syst. Biol. doi: 10.1038/msb.2008.80 – volume: 16 start-page: 1950 year: 2006 ident: C0MB00004C-(cit15)/*[position()=1] publication-title: Curr. Biol. doi: 10.1016/j.cub.2006.08.026 – volume: 10 start-page: 265 year: 2009 ident: C0MB00004C-(cit8)/*[position()=1] publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2653 – volume: 185 start-page: 193 year: 2009 ident: C0MB00004C-(cit2)/*[position()=1] publication-title: J. Cell Biol. doi: 10.1083/jcb.200812045 – volume: 8 start-page: 547 year: 2009 ident: C0MB00004C-(cit24)/*[position()=1] publication-title: Nat. Rev. Drug Discovery doi: 10.1038/nrd2907 – volume: 20 start-page: 77 year: 2008 ident: C0MB00004C-(cit16)/*[position()=1] publication-title: Curr. Opin. Cell Biol. doi: 10.1016/j.ceb.2007.11.008 – volume: 27 start-page: 659 year: 2009 ident: C0MB00004C-(cit53)/*[position()=1] publication-title: Nat. Biotechnol. doi: 10.1038/nbt.1549 – volume: 18 start-page: 4972 year: 2008 ident: C0MB00004C-(cit22)/*[position()=1] publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2008.08.033 – volume: 89 start-page: 149 year: 2000 ident: C0MB00004C-(cit48)/*[position()=1] publication-title: Math. Program. doi: 10.1007/PL00011391 – volume: 321 start-page: 126 year: 2008 ident: C0MB00004C-(cit58)/*[position()=1] publication-title: Science doi: 10.1126/science.1156951 – volume: 2 start-page: ra31 year: 2009 ident: C0MB00004C-(cit27)/*[position()=1] publication-title: Sci. Signaling doi: 10.1126/scisignal.2000352 – volume: 8 start-page: 450 year: 2007 ident: C0MB00004C-(cit59)/*[position()=1] publication-title: Nat. Rev. Genet. doi: 10.1038/nrg2102 – volume: 4 start-page: 11 year: 2010 ident: C0MB00004C-(cit49)/*[position()=1] publication-title: BMC Syst. Biol. doi: 10.1186/1752-0509-4-11 – volume: 58 start-page: 1467 year: 2008 ident: C0MB00004C-(cit47)/*[position()=1] publication-title: Appl. Numer. Math. doi: 10.1016/j.apnum.2007.09.001 – volume: 102 start-page: 11663 year: 2005 ident: C0MB00004C-(cit33)/*[position()=1] publication-title: Proc. Natl. Acad. Sci. U. S. A. doi: 10.1073/pnas.0500410102 – volume: 4 start-page: 927 year: 2004 ident: C0MB00004C-(cit51)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc1502 – volume: 6 start-page: 202 year: 2007 ident: C0MB00004C-(cit52)/*[position()=1] publication-title: Nat. Rev. Drug Discovery doi: 10.1038/nrd2195 – volume: 297 start-page: 63 year: 2002 ident: C0MB00004C-(cit60)/*[position()=1] publication-title: Science doi: 10.1126/science.1073096 – volume: 5 start-page: 239 year: 2008 ident: C0MB00004C-(cit45)/*[position()=1] publication-title: Mol. Syst. Biol. doi: 10.1038/msb.2008.74 – volume: 5 start-page: 1569 year: 2009 ident: C0MB00004C-(cit57)/*[position()=1] publication-title: Mol. BioSyst. doi: 10.1039/b907562n – volume: 181 start-page: 65 year: 2008 ident: C0MB00004C-(cit34)/*[position()=1] publication-title: J. Cell Biol. doi: 10.1083/jcb.200712027 – volume: 39 start-page: 9494 year: 2000 ident: C0MB00004C-(cit31)/*[position()=1] publication-title: Biochemistry doi: 10.1021/bi0009643 – volume: 10 start-page: 130 year: 2010 ident: C0MB00004C-(cit62)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2787 – volume: 320 start-page: 1655 year: 2008 ident: C0MB00004C-(cit9)/*[position()=1] publication-title: Science doi: 10.1126/science.1157425 – volume: 10 start-page: 262 year: 2004 ident: C0MB00004C-(cit55)/*[position()=1] publication-title: Nat. Med. doi: 10.1038/nm1003 – volume: 65 start-page: 7037 year: 2005 ident: C0MB00004C-(cit37)/*[position()=1] publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-05-1054 – volume: 28 start-page: 27 year: 2000 ident: C0MB00004C-(cit28)/*[position()=1] publication-title: Nucleic Acids Res. doi: 10.1093/nar/28.1.27 – volume: 5 start-page: 246 year: 2009 ident: C0MB00004C-(cit46)/*[position()=1] publication-title: Mol. Syst. Biol. doi: 10.1038/msb.2009.4 – volume: 6 start-page: 264 year: 2010 ident: C0MB00004C-(cit19)/*[position()=1] publication-title: Mol. BioSyst. doi: 10.1039/B907863K – volume: 23 start-page: 319 year: 2006 ident: C0MB00004C-(cit43)/*[position()=1] publication-title: Mol. Cell doi: 10.1016/j.molcel.2006.06.013 – volume: 52 start-page: 2629 year: 2009 ident: C0MB00004C-(cit23)/*[position()=1] publication-title: J. Med. Chem. doi: 10.1021/jm8012129 – volume: 9 start-page: 153 year: 2009 ident: C0MB00004C-(cit1)/*[position()=1] publication-title: Nat. Rev. Cancer doi: 10.1038/nrc2602 – volume: 136 start-page: 823 year: 2009 ident: C0MB00004C-(cit61)/*[position()=1] publication-title: Cell doi: 10.1016/j.cell.2009.02.024 – volume: 33 start-page: D428 year: 2004 ident: C0MB00004C-(cit29)/*[position()=1] publication-title: Nucleic Acids Res. doi: 10.1093/nar/gki072 – volume: 23 start-page: 307 year: 2006 ident: C0MB00004C-(cit38)/*[position()=1] publication-title: Mol. Cell doi: 10.1016/j.molcel.2006.06.016 – volume: 15 start-page: 345 year: 1995 ident: C0MB00004C-(cit50)/*[position()=1] publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.15.1.345 – volume: 455 start-page: 119 year: 2008 ident: C0MB00004C-(cit10)/*[position()=1] publication-title: Nature doi: 10.1038/nature07185 – volume: 10 start-page: 424 year: 2009 ident: C0MB00004C-(cit17)/*[position()=1] publication-title: Briefings Bioinf. doi: 10.1093/bib/bbp005 |
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| SubjectTerms | Algorithms Aurora Kinases Blotting, Western Cell Cycle - physiology Cell Cycle Proteins - antagonists & inhibitors Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Survival - drug effects Cell Survival - genetics Computational Biology Enzyme Inhibitors - pharmacology HeLa Cells Humans Models, Biological Polo-Like Kinase 1 Protein Serine-Threonine Kinases - antagonists & inhibitors Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins - antagonists & inhibitors Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism |
| Title | Integrated computational model of cell cycle and checkpoint reveals different essential roles of Aurora-A and Plk1 in mitotic entry |
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