KEGG   PATHWAY: bbub04110
Entry
bbub04110                   Pathway                                
Name
Cell cycle - Bubalus bubalis (water buffalo)
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
bbub04110  Cell cycle
bbub04110

Other DBs
GO: 0000278
Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102389005  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
102389227  NIPBL; nipped-B-like protein isoform X5 [KO:K06672]
102389416  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
102389419  [KO:K26116]
102389707  DDX11; ATP-dependent DNA helicase DDX11 isoform X2 [KO:K11273] [EC:3.6.4.13]
102389770  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
102389933  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
102390519  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
102390629  TGFB2; transforming growth factor beta-2 proprotein isoform X3 [KO:K13376]
102390759  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
102390834  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
102390852  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
102390979  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
102391097  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
102391571  CDC14B; dual specificity protein phosphatase CDC14B isoform X17 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102391813  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
102392228  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
102392555  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
102392639  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102392759  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
102392926  YWHAQ; 14-3-3 protein theta [KO:K16197]
102393446  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
102393543  DBF4; protein DBF4 homolog A isoform X3 [KO:K06629]
102393627  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
102394197  EP300; histone acetyltransferase p300 isoform X4 [KO:K04498] [EC:2.3.1.48]
102394305  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102394552  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
102394623  HDAC8; histone deacetylase 8 isoform X2 [KO:K11405] [EC:3.5.1.98]
102394833  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
102394964  KNL1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
102395106  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
102395797  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
102395935  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
102396050  [KO:K16197]
102396289  ORC6; origin recognition complex subunit 6 [KO:K02608]
102396397  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102396473  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
102396508  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
102396672  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
102396778  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
102397026  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
102397136  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
102397386  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
102397540  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
102397735  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
102397948  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102398229  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
102398457  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102398465  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102398478  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
102398540  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X2 [KO:K11584]
102398715  CCNA2; cyclin-A2 [KO:K06627]
102398790  SFN; 14-3-3 protein sigma [KO:K06644]
102398989  TTK; dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
102399207  ATM; serine-protein kinase ATM isoform X2 [KO:K04728] [EC:2.7.11.1]
102399947  YWHAH; 14-3-3 protein eta [KO:K16198]
102400134  RB1; retinoblastoma-associated protein [KO:K06618]
102400333  BUB3; mitotic checkpoint protein BUB3 isoform X3 [KO:K02180]
102400493  CUL1; cullin-1 [KO:K03347]
102400710  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102400806  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102400979  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
102400980  [KO:K03347]
102401080  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
102401152  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
102401483  CDC16; cell division cycle protein 16 homolog [KO:K03353]
102401535  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
102401554  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
102401819  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
102401862  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102401884  ATRX; transcriptional regulator ATRX isoform X6 [KO:K10779]
102401934  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102401972  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
102402069  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
102402664  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
102402745  CDC14A; dual specificity protein phosphatase CDC14A isoform X6 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102402820  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
102402827  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
102403077  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102403201  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X3 [KO:K11267]
102403332  E2F2; transcription factor E2F2 [KO:K09389]
102403670  TICRR; treslin [KO:K26117]
102403750  [KO:K04498] [EC:2.3.1.48]
102403793  SMC1A; structural maintenance of chromosomes protein 1A isoform X3 [KO:K06636]
102404816  [KO:K12456]
102405000  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
102405130  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
102405261  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
102405775  CDC45; cell division control protein 45 homolog isoform X2 [KO:K06628]
102405897  [KO:K04682]
102405957  CDK1; cyclin-dependent kinase 1 isoform X3 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102406138  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102406311  [KO:K06621]
102406434  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102406564  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102406712  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
102406954  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102407021  YWHAG; 14-3-3 protein gamma [KO:K16198]
102407100  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
102407325  CDK6; cyclin-dependent kinase 6 isoform X2 [KO:K02091] [EC:2.7.11.22]
102407397  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102407405  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
102407460  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102407714  PLK1; serine/threonine-protein kinase PLK1 isoform X2 [KO:K06631] [EC:2.7.11.21]
102407953  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
102407990  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
102408087  CCNA1; cyclin-A1 [KO:K06627]
102408224  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102409212  ORC1; origin recognition complex subunit 1 [KO:K02603]
102409320  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
102409445  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
102409762  CDT1; DNA replication factor Cdt1 [KO:K10727]
102409889  CDC20; cell division cycle protein 20 homolog [KO:K03363]
102410004  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102410020  SGO1; shugoshin 1 [KO:K11580]
102410072  ORC2; origin recognition complex subunit 2 [KO:K02604]
102410115  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102410141  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
102410223  PCNA; proliferating cell nuclear antigen [KO:K04802]
102410421  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
102410587  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102410717  [KO:K03094]
102411133  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102411391  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
102411533  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
102411610  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X22 [KO:K11584]
102411655  CDC6; cell division control protein 6 homolog isoform X2 [KO:K02213]
102411827  [KO:K17390]
102411842  CDK7; cyclin-dependent kinase 7 isoform X4 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102411892  [KO:K26093]
102411932  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
102412107  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102412327  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
102412395  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102412546  [KO:K03456]
102412776  ORC5; origin recognition complex subunit 5 isoform X2 [KO:K02607]
102412787  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102412869  [KO:K03456]
102413044  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
102413631  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X2 [KO:K06679]
102413660  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
102413755  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
102414091  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
102414330  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
102414522  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102414672  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
102414782  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
102415084  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
102415135  CCNH; cyclin-H isoform X3 [KO:K06634]
102415292  DBF4B; protein DBF4 homolog B isoform X3 [KO:K06629]
102415397  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
102415423  PTTG1; securin isoform X2 [KO:K06635]
102415490  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
102415730  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
102415951  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102416097  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
102416300  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
102416566  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
102416592  WAPL; wings apart-like protein homolog isoform X2 [KO:K25163]
102416611  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
112577629  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
112586263  MAD2L1; LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
123464883  E2F1; transcription factor E2F1 [KO:K17454]
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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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.
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Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
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Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
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)
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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
  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)
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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
  Title
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.
  Title
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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Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
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Nature 408:307-10 (2000)
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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)
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Reference
PMID:9029154
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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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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
  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
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
bbub03030  DNA replication
bbub04010  MAPK signaling pathway
bbub04120  Ubiquitin mediated proteolysis
bbub04210  Apoptosis
KO pathway
ko04110   

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