KEGG   PATHWAY: fca04110
Entry
fca04110                    Pathway                                
Name
Cell cycle - Felis catus (domestic cat)
Description
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated.
 Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation.
Class
Cellular Processes; Cell growth and death
Pathway map
fca04110  Cell cycle
fca04110

Other DBs
GO: 0000278
Organism
Felis catus (domestic cat) [GN:fca]
Gene
100037407  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100037415  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100127113  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
100379628  MYC; myc proto-oncogene protein [KO:K04377]
101080283  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
101080704  PCNA; proliferating cell nuclear antigen [KO:K04802]
101080972  CCNB2; G2/mitotic-specific cyclin-B2 isoform X3 [KO:K21770]
101081075  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101081164  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X4 [KO:K11584]
101081264  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
101081331  ANAPC16; anaphase-promoting complex subunit 16 isoform X2 [KO:K25229]
101081660  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101081706  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
101081728  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
101081785  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
101082367  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
101082430  STAG1; cohesin subunit SA-1 isoform X2 [KO:K06671]
101082786  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101082791  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
101083033  CDCA5; sororin isoform X3 [KO:K17390]
101083266  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101083365  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101083515  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
101083726  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101083734  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
101084045  [KO:K03094]
101084118  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
101084156  YWHAG; 14-3-3 protein gamma [KO:K16198]
101084353  ANAPC1; anaphase-promoting complex subunit 1 isoform X2 [KO:K03348]
101084390  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101084421  PTTG1; securin isoform X1 [KO:K06635]
101084723  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
101084987  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
101084992  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
101085035  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
101085227  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101085293  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101085347  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
101085426  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
101085449  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
101085665  CHEK2; serine/threonine-protein kinase Chk2 isoform X3 [KO:K06641] [EC:2.7.11.1]
101085739  ORC2; origin recognition complex subunit 2 [KO:K02604]
101085761  DBF4B; LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
101086024  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
101086096  CDC14B; dual specificity protein phosphatase CDC14B isoform X6 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101086192  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
101086284  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
101086398  KNL1; kinetochore scaffold 1 [KO:K11542]
101086445  CDC23; cell division cycle protein 23 homolog [KO:K03355]
101086509  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101086543  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
101086582  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101086781  CDK7; cyclin-dependent kinase 7 isoform X3 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101086802  ANAPC10; anaphase-promoting complex subunit 10 isoform X5 [KO:K03357]
101086942  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
101087014  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101087051  CUL1; cullin-1 isoform X3 [KO:K03347]
101087179  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101087501  SFN; 14-3-3 protein sigma [KO:K06644]
101087622  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101087628  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
101087670  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
101087758  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101087946  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
101087971  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101088023  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
101088059  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
101088165  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
101088344  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
101088383  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101088389  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
101088481  YWHAQ; 14-3-3 protein theta [KO:K16197]
101088513  TFDP2; transcription factor Dp-2 isoform X2 [KO:K09392]
101088573  CCNA2; cyclin-A2 [KO:K06627]
101088601  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101089013  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
101089189  MAD2L1BP; MAD2L1-binding protein isoform X1 [KO:K26093]
101089220  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
101089291  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
101089576  MCM4; DNA replication licensing factor MCM4 isoform X2 [KO:K02212] [EC:5.6.2.3]
101089768  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
101090017  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
101090158  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
101090170  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
101090176  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101090870  TICRR; treslin isoform X1 [KO:K26117]
101090883  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
101090950  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101091234  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
101091685  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101091765  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101091838  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
101091897  WEE1; wee1-like protein kinase isoform X2 [KO:K06632] [EC:2.7.11.1]
101092703  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101092757  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
101092821  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
101092847  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101092865  MCM5; DNA replication licensing factor MCM5 isoform X1 [KO:K02209] [EC:5.6.2.3]
101093092  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
101093211  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
101093300  BUB3; mitotic checkpoint protein BUB3 isoform X4 [KO:K02180]
101093305  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
101093351  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101093368  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
101093414  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
101093650  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101093897  [KO:K16197]
101094427  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X2 [KO:K11584]
101094471  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101094667  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101095164  RBL1; retinoblastoma-like protein 1 isoform X2 [KO:K04681]
101095398  CCNH; cyclin-H isoform X2 [KO:K06634]
101095692  CDC26; anaphase-promoting complex subunit CDC26 isoform X2 [KO:K03359]
101095950  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
101096213  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
101096383  HDAC8; histone deacetylase 8 isoform X8 [KO:K11405] [EC:3.5.1.98]
101096875  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
101097259  CDC20; cell division cycle protein 20 homolog isoform X2 [KO:K03363]
101097519  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
101097815  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
101097858  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101097903  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
101097998  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
101098067  E2F2; transcription factor E2F2 [KO:K09389]
101098126  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
101098358  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
101098406  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
101098425  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
101098445  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101098454  E2F1; transcription factor E2F1 isoform X3 [KO:K17454]
101098469  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101098508  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101098673  CDT1; DNA replication factor Cdt1 [KO:K10727]
101098911  E2F4; transcription factor E2F4 [KO:K04682]
101099017  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101099179  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
101099228  HDAC1; histone deacetylase 1 isoform X3 [KO:K06067] [EC:3.5.1.98]
101099271  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101099275  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
101099442  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101099643  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101099908  YWHAH; 14-3-3 protein eta [KO:K16198]
101100662  SGO1; shugoshin 1 [KO:K11580]
101101311  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101101356  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
101101387  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101101425  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101101566  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
101101592  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101101657  [KO:K06635]
101101670  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
102900567  [KO:K05868]
102900654  [KO:K06630]
102901065  SMC1B; structural maintenance of chromosomes protein 1B isoform X2 [KO:K06636]
102901245  [KO:K06671]
105261011  CDKN1C; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1C [KO:K09993]
493847  TP53; cellular tumor antigen p53 [KO:K04451]
493939  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
493943  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
493958  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
768263  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
Reference
PMID:7908906
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Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
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J Biol Chem 269:11030-6 (1994)
Reference
PMID:8242749
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Welch PJ, Wang JY
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A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
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Cell 75:779-90 (1993)
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Reference
PMID:16936746
  Authors
Macaluso M, Montanari M, Giordano A
  Title
Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes.
  Journal
Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
Oncogene 24:2796-809 (2005)
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Reference
PMID:17568790
  Authors
Boutros R, Lobjois V, Ducommun B
  Title
CDC25 phosphatases in cancer cells: key players? Good targets?
  Journal
Nat Rev Cancer 7:495-507 (2007)
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Reference
PMID:9832503
  Authors
Diehl JA, Cheng M, Roussel MF, Sherr CJ
  Title
Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.
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Genes Dev 12:3499-511 (1998)
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Reference
PMID:19020303
  Authors
Klein EA, Assoian RK
  Title
Transcriptional regulation of the cyclin D1 gene at a glance.
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J Cell Sci 121:3853-7 (2008)
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Reference
PMID:10385618
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Sherr CJ, Roberts JM
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CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
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Reference
PMID:12809600
  Authors
Shi Y, Massague J.
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Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
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Cell 113:685-700 (2003)
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Reference
PMID:12925736
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Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, Hatakeyama S, Nakayama K, Nakayama KI
  Title
Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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Reference
PMID:16212951
  Authors
Bond M, Sala-Newby GB, Wu YJ, Newby AC
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Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
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Cardiovasc Res 69:198-206 (2006)
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Reference
PMID:15838523
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Harris SL, Levine AJ.
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The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
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Reference
PMID:11099028
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Surfing the p53 network.
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Nature 408:307-10 (2000)
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Reference
PMID:7973727
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Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
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Science 266:1376-80 (1994)
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Reference
PMID:9889196
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Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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EMBO J 18:396-410 (1999)
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Reference
PMID:17018296
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Sheu YJ, Stillman B
  Title
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
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Mol Cell 24:101-13 (2006)
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Reference
PMID:9029154
  Authors
Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M
  Title
Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity.
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EMBO J 16:343-54 (1997)
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Reference
PMID:15876871
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Lolli G, Johnson LN
  Title
CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?
  Journal
Cell Cycle 4:572-7 (2005)
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Reference
PMID:17426725
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
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Nat Rev Mol Cell Biol 8:379-93 (2007)
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Reference
PMID:12573239
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  Title
Chromosome cohesion and separation: from men and molecules.
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Curr Biol 13:R104-14 (2003)
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Reference
PMID:15568976
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Stegmeier F, Amon A
  Title
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
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Annu Rev Genet 38:203-32 (2004)
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Reference
PMID:9618481
  Authors
Moustakas A, Kardassis D
  Title
Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
  Journal
Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
PMID:26650195
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de Boer HR, Guerrero Llobet S, van Vugt MA
  Title
Controlling the response to DNA damage by the APC/C-Cdh1.
  Journal
Cell Mol Life Sci 73:949-60 (2016)
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Reference
PMID:20935501
  Authors
Qiao X, Zhang L, Gamper AM, Fujita T, Wan Y
  Title
APC/C-Cdh1: from cell cycle to cellular differentiation and genomic integrity.
  Journal
Cell Cycle 9:3904-12 (2010)
DOI:10.4161/cc.9.19.13585
Related
pathway
fca03030  DNA replication
fca04010  MAPK signaling pathway
fca04120  Ubiquitin mediated proteolysis
fca04210  Apoptosis
KO pathway
ko04110   

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