KEGG   PATHWAY: ecb04110
Entry
ecb04110                    Pathway                                
Name
Cell cycle - Equus caballus (horse)
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
ecb04110  Cell cycle
ecb04110

Other DBs
GO: 0000278
Organism
Equus caballus (horse) [GN:ecb]
Gene
100033843  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100033845  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100033846  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100033900  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
100034122  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100049841  ORC6; origin recognition complex subunit 6 [KO:K02608]
100049964  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100050093  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100050269  BUB3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
100050313  DBF4; protein DBF4 homolog A isoform X3 [KO:K06629]
100050377  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100050436  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X2 [KO:K10500]
100050735  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
100050871  CDC45; cell division control protein 45 homolog isoform X2 [KO:K06628]
100050887  CDCA5; sororin isoform X10 [KO:K17390]
100051005  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100051122  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
100051139  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
100051150  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100051195  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
100051217  CUL1; cullin-1 [KO:K03347]
100051228  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
100051303  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
100051405  TFDP2; transcription factor Dp-2 isoform X8 [KO:K09392]
100051765  TGFB3; transforming growth factor beta-3 [KO:K13377]
100051790  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100051869  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
100051935  SGO1; shugoshin 1 isoform X2 [KO:K11580]
100051948  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
100052065  PCNA; proliferating cell nuclear antigen [KO:K04802]
100052084  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100052248  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100052401  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
100052425  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
100052492  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
100052524  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
100053101  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
100053119  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
100053266  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
100053348  CDC20; cell division cycle protein 20 homolog [KO:K03363]
100053547  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
100053690  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
100053697  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
100053882  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100054340  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
100054413  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
100054440  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
100054552  CDC27; cell division cycle protein 27 homolog isoform X6 [KO:K03350]
100054880  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100054977  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X6 [KO:K11584]
100054996  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100055046  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
100055053  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
100055302  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100055413  MAD2L1BP; MAD2L1-binding protein isoform X1 [KO:K26093]
100055572  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
100055581  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
100055626  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
100055766  CDC14A; dual specificity protein phosphatase CDC14A isoform X6 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100055921  ORC4; origin recognition complex subunit 4 isoform X2 [KO:K02606]
100056060  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
100056084  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
100056139  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
100057080  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
100057082  SFN; 14-3-3 protein sigma [KO:K06644]
100057123  YWHAQ; 14-3-3 protein theta [KO:K16197]
100057138  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
100057261  MTBP; mdm2-binding protein isoform X2 [KO:K26116]
100057750  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
100057866  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
100057897  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
100058376  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
100058548  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
100058743  ORC5; origin recognition complex subunit 5 isoform X6 [KO:K02607]
100058904  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
100059288  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
100059335  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
100059640  PTTG1; securin isoform X1 [KO:K06635]
100059731  YWHAG; 14-3-3 protein gamma [KO:K16198]
100059767  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
100059768  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100059962  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100060431  RBL2; retinoblastoma-like protein 2 isoform X2 [KO:K16332]
100060468  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
100060473  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
100060754  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
100061033  GSK3B; glycogen synthase kinase-3 beta isoform X6 [KO:K03083] [EC:2.7.11.26]
100061287  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
100061625  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
100061736  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
100061765  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100061980  ORC1; origin recognition complex subunit 1 [KO:K02603]
100062044  TP53; cellular tumor antigen p53 [KO:K04451]
100062224  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100062249  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
100062352  CDC25C; M-phase inducer phosphatase 3 isoform X3 [KO:K05867] [EC:3.1.3.48]
100062379  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100062529  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
100062627  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100062649  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
100062837  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
100062878  YWHAH; 14-3-3 protein eta [KO:K16198]
100062946  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100063155  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
100063779  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
100063999  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X4 [KO:K11267]
100064022  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100064049  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
100064223  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
100064353  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100064370  DBF4B; protein DBF4 homolog B isoform X2 [KO:K06629]
100065185  CCNH; cyclin-H isoform X1 [KO:K06634]
100065497  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
100065530  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100065661  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
100066027  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
100066106  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
100066590  CCND3; G1/S-specific cyclin-D3 isoform X3 [KO:K10152]
100067388  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
100067788  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
100067880  ORC2; origin recognition complex subunit 2 [KO:K02604]
100068097  MYC; myc proto-oncogene protein [KO:K04377]
100068388  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100068673  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
100068871  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
100069108  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
100069163  TFDP1; transcription factor Dp-1 [KO:K04683]
100069192  E2F1; transcription factor E2F1 [KO:K17454]
100069285  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
100069586  TTK; dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
100069613  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100069681  TICRR; treslin [KO:K26117]
100069690  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
100069715  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100069786  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100070281  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100070408  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100071182  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
100071354  KNL1; kinetochore scaffold 1 isoform X1 [KO:K11542]
100072219  CCNA2; cyclin-A2 [KO:K06627]
100072299  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100072353  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A isoform X1 [KO:K02537]
100072578  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100072599  CDC23; cell division cycle protein 23 homolog [KO:K03355]
100072678  ATRX; transcriptional regulator ATRX isoform X3 [KO:K10779]
100072806  ANAPC16; anaphase-promoting complex subunit 16 isoform X2 [KO:K25229]
100073050  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
100146270  [KO:K06621]
100147188  CCNA1; cyclin-A1 [KO:K06627]
100629735  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
100630277  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
100630299  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102149114  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111767487  [KO:K03348]
111768045  [KO:K03348]
111771316  [KO:K13376]
111773925  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
791233  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
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)
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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
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Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes.
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Oncogene 25:5263-7 (2006)
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Reference
PMID:15838516
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Cobrinik D
  Title
Pocket proteins and cell cycle control.
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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?
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Nat Rev Cancer 7:495-507 (2007)
DOI:10.1038/nrc2169
Reference
PMID:9832503
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Diehl JA, Cheng M, Roussel MF, Sherr CJ
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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
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Klein EA, Assoian RK
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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)
DOI:10.1101/gad.13.12.1501
Reference
PMID:12809600
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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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PMID:7973727
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Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
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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
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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
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Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M
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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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CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?
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Cell Cycle 4:572-7 (2005)
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Reference
PMID:17426725
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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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Uhlmann F
  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
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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
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Moustakas A, Kardassis D
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Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
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Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
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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.
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Cell Mol Life Sci 73:949-60 (2016)
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Reference
PMID:20935501
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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
ecb03030  DNA replication
ecb04010  MAPK signaling pathway
ecb04120  Ubiquitin mediated proteolysis
ecb04210  Apoptosis
KO pathway
ko04110   

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