KEGG   PATHWAY: bom04110
Entry
bom04110                    Pathway                                
Name
Cell cycle - Bos mutus (wild yak)
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
bom04110  Cell cycle
bom04110

Other DBs
GO: 0000278
Organism
Bos mutus (wild yak) [GN:bom]
Gene
102264536  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
102264757  BUB3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
102264880  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102264992  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102265183  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
102265469  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
102265567  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
102265764  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
102265995  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
102266065  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102266238  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
102266301  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102266347  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102266500  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102266978  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102267169  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102267315  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
102267511  [KO:K16197]
102267970  TICRR; treslin [KO:K26117]
102268077  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102268181  E2F2; transcription factor E2F2 [KO:K09389]
102268491  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102268672  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102268676  WAPL; wings apart-like protein homolog isoform X2 [KO:K25163]
102269341  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
102269484  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
102269506  TFDP2; transcription factor Dp-2 isoform X5 [KO:K09392]
102269700  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
102270486  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
102270512  ORC4; origin recognition complex subunit 4 [KO:K02606]
102270546  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102270577  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
102270876  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102271096  CDC14A; dual specificity protein phosphatase CDC14A isoform X7 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102271261  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
102271403  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
102271499  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
102271554  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102271624  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
102272027  CDC45; cell division control protein 45 homolog isoform X2 [KO:K06628]
102272163  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
102272370  TP53; cellular tumor antigen p53 [KO:K04451]
102272454  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
102272576  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102272719  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X3 [KO:K03868] [EC:2.3.2.32]
102273007  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102273137  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
102273235  SFN; 14-3-3 protein sigma [KO:K06644]
102273578  [KO:K16197]
102273917  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
102274304  MYC; LOW QUALITY PROTEIN: myc proto-oncogene protein [KO:K04377]
102274455  CCNA2; cyclin-A2 [KO:K06627]
102274479  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
102274816  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
102274863  E2F1; transcription factor E2F1 [KO:K17454]
102275068  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
102275205  CDC16; cell division cycle protein 16 homolog [KO:K03353]
102275260  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102275388  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
102275397  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
102275413  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
102275543  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
102275633  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
102275872  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
102275950  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
102276116  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102276245  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102276514  CCNA1; cyclin-A1 [KO:K06627]
102276528  [KO:K25228]
102276553  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
102276738  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
102276816  TFDP1; transcription factor Dp-1 [KO:K04683]
102276872  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
102277344  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
102277351  PCNA; proliferating cell nuclear antigen [KO:K04802]
102277447  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
102277514  CUL1; cullin-1 [KO:K03347]
102277651  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
102277877  ORC1; origin recognition complex subunit 1 [KO:K02603]
102278053  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
102278065  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102278163  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
102278265  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102278282  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
102278310  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
102278545  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102278567  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102278583  [KO:K03456]
102278832  YWHAQ; 14-3-3 protein theta [KO:K16197]
102278849  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
102278968  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102279151  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
102279156  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102279360  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
102279373  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
102279522  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102279559  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
102279602  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102279794  KNL1; LOW QUALITY PROTEIN: outer kinetochore KNL1 complex subunit KNL1 [KO:K11542]
102279855  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
102280324  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
102280663  CDT1; LOW QUALITY PROTEIN: DNA replication factor Cdt1 [KO:K10727]
102280797  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
102280893  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
102281115  STAG1; cohesin subunit SA-1 [KO:K06671]
102281541  PTTG1; securin isoform X1 [KO:K06635]
102281545  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
102281676  E2F5; transcription factor E2F5 [KO:K04682]
102281734  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
102281744  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
102281976  YWHAG; 14-3-3 protein gamma [KO:K16198]
102282012  ORC5; origin recognition complex subunit 5 [KO:K02607]
102282280  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
102282426  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
102282540  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102282627  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
102282840  SGO1; shugoshin 1 [KO:K11580]
102283101  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
102283357  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
102283491  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102283552  CHEK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
102283808  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102284153  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
102284230  TTK; LOW QUALITY PROTEIN: dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
102284437  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
102284557  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
102284697  CCNE2; LOW QUALITY PROTEIN: G1/S-specific cyclin-E2 [KO:K06626]
102284975  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
102285046  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
102285117  [KO:K06635]
102285120  SMC1A; structural maintenance of chromosomes protein 1A isoform X2 [KO:K06636]
102285183  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
102285185  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
102285512  CCNB2; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B2 [KO:K21770]
102285720  CDCA5; sororin [KO:K17390]
102285773  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
102285850  CDC14B; dual specificity protein phosphatase CDC14B isoform X10 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102285992  PRKDC; LOW QUALITY PROTEIN: DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
102286105  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102286266  CDC23; cell division cycle protein 23 homolog [KO:K03355]
102286353  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
102286395  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
102286495  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102286579  CDC20; cell division cycle protein 20 homolog [KO:K03363]
102286646  MCM7; DNA replication licensing factor MCM7 isoform X2 [KO:K02210] [EC:5.6.2.3]
102287071  CDK1; cyclin-dependent kinase 1 isoform X2 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102287083  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
102287197  YWHAH; 14-3-3 protein eta [KO:K16198]
102287313  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
102287359  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
102287490  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
102287616  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
102287767  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102287801  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
102287978  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
102288000  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102288145  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102288323  CCNH; cyclin-H isoform X9 [KO:K06634]
138984770  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
138987538  [KO:K06632] [EC:2.7.11.1]
138988920  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
Reference
PMID:7908906
  Authors
Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
  Journal
J Biol Chem 269:11030-6 (1994)
Reference
PMID:8242749
  Authors
Welch PJ, Wang JY
  Title
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)
DOI:10.1016/0092-8674(93)90497-E
Reference
PMID:16936746
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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.
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Oncogene 24:2796-809 (2005)
DOI:10.1038/sj.onc.1208619
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
  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)
DOI:10.1101/gad.12.22.3499
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
  Authors
Sherr CJ, Roberts JM
  Title
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)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:12925736
  Authors
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)
DOI:10.1016/j.cardiores.2005.08.020
Reference
PMID:15838523
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11099028
  Authors
Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
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Nature 408:307-10 (2000)
DOI:10.1038/35042675
Reference
PMID:7973727
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Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
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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)
DOI:10.1016/j.molcel.2006.07.033
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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Reference
PMID:15876871
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  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
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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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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
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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.
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Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
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  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
  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
bom03030  DNA replication
bom04010  MAPK signaling pathway
bom04120  Ubiquitin mediated proteolysis
bom04210  Apoptosis
KO pathway
ko04110   

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