KEGG   PATHWAY: onl04110
Entry
onl04110                    Pathway                                
Name
Cell cycle - Oreochromis niloticus (Nile tilapia)
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
onl04110  Cell cycle
onl04110

Other DBs
GO: 0000278
Organism
Oreochromis niloticus (Nile tilapia) [GN:onl]
Gene
100691373  G1/S-specific cyclin-D1 [KO:K04503]
100691051  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
100707642  G1/S-specific cyclin-D2 [KO:K10151]
100712090  G1/S-specific cyclin-D2 [KO:K10151]
100698323  G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
100690263  G1/S-specific cyclin-D2 isoform X1 [KO:K10152]
100710125  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100711614  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100695113  cyclin-dependent kinase 4 isoform X1 [KO:K02091] [EC:2.7.11.22]
100708745  rb1; retinoblastoma-associated protein [KO:K06618]
100712326  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K04681]
100699851  rbl1; retinoblastoma-like protein 1 [KO:K04681]
100692495  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100709901  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100711924  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
100691799  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
100697280  hdac2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
100697698  e2f1; transcription factor E2F1 [KO:K17454]
100691560  e2f2; transcription factor E2F2 isoform X2 [KO:K09389]
100704871  transcription factor E2F3 [KO:K06620]
100698567  e2f3; transcription factor E2F3 isoform X1 [KO:K06620]
100699665  transcription factor E2F5 isoform X1 [KO:K04682]
100709880  e2f4; transcription factor E2F4 [KO:K04682]
100705578  transcription factor E2F5 isoform X1 [KO:K04682]
100703369  tfdp1; transcription factor Dp-1 [KO:K04683]
100712404  gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100694653  tgfb1a; transforming growth factor, beta 1a precursor [KO:K13375]
100707856  tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100690458  transforming growth factor beta-2 [KO:K13376]
100710008  transforming growth factor beta-3 [KO:K13377]
100712568  tgfb3; transforming growth factor beta-3 [KO:K13377]
100693777  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100710325  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100692385  mothers against decapentaplegic homolog 3 [KO:K23605]
100695277  smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100693833  mothers against decapentaplegic homolog 4 [KO:K04501]
100705094  mothers against decapentaplegic homolog 4 isoform X2 [KO:K04501]
100700558  mothers against decapentaplegic homolog 4 [KO:K04501]
100708381  mothers against decapentaplegic homolog 4 [KO:K04501]
100693620  transcriptional regulator Myc-A [KO:K04377]
100689989  myc; myc proto-oncogene protein [KO:K04377]
100703314  transcriptional regulator Myc-2 [KO:K04377]
100703107  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
100707378  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100695802  cyclin-dependent kinase 4 inhibitor C isoform X1 [KO:K06622]
109194384  cyclin-dependent kinase 4 inhibitor C isoform X2 [KO:K06622]
100699210  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
102083324  cyclin-dependent kinase inhibitor 1B [KO:K06624]
100709597  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100703282  cyclin-dependent kinase inhibitor 1B [KO:K09993]
100711644  cyclin-dependent kinase inhibitor 1C [KO:K09993]
102082412  cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
100698501  cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
100692568  G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
100696937  ccne1; LOW QUALITY PROTEIN: G1/S-specific cyclin-E1 [KO:K06626]
102075526  G1/S-specific cyclin-E3 isoform X2 [KO:K06626]
100706903  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100697275  skp1; S-phase kinase-associated protein 1 [KO:K03094]
100699353  cul1; cullin-1 [KO:K03347]
100696705  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100695272  skp2; S-phase kinase-associated protein 2 [KO:K03875]
100711022  ccna2; cyclin-A2 [KO:K06627]
100707677  ccna1; cyclin-A1 [KO:K06627]
100701578  cdc6; cell division control protein 6 homolog [KO:K02213]
100693026  cdt1; DNA replication factor Cdt1 [KO:K10727]
100711211  orc1; origin recognition complex subunit 1 [KO:K02603]
100701051  orc2; origin recognition complex subunit 2 [KO:K02604]
100710607  orc3; origin recognition complex subunit 3 [KO:K02605]
100709785  orc4; origin recognition complex subunit 4 [KO:K02606]
100706845  orc5; origin recognition complex subunit 5 [KO:K02607]
100693703  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
100697228  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
100697842  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
100710836  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
100693300  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
100710845  mcm7; LOW QUALITY PROTEIN: DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
100701026  cdc45; cell division control protein 45 homolog [KO:K06628]
100699511  ticrr; treslin isoform X1 [KO:K26117]
100696174  mtbp; mdm2-binding protein isoform X1 [KO:K26116]
100698986  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
100699585  dbf4; protein DBF4 homolog A [KO:K06629]
100707794  uncharacterized protein LOC100707794 [KO:K06629]
100702661  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100708411  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100692470  G2/mitotic-specific cyclin-B2 isoform X2 [KO:K21770]
100534580  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
100711118  cdc25b; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
100710156  14-3-3 protein beta/alpha [KO:K16197]
100700668  14-3-3 protein beta/alpha-1 [KO:K16197]
100689836  14-3-3 protein beta/alpha-A [KO:K16197]
100691663  14-3-3 protein zeta/delta [KO:K16197]
100703537  14-3-3 protein beta/alpha-A [KO:K16197]
100689869  14-3-3 protein epsilon isoform X1 [KO:K06630]
100704829  14-3-3 protein epsilon isoform X1 [KO:K06630]
100705716  14-3-3 protein gamma-1 isoform X1 [KO:K16198]
100700540  14-3-3 protein gamma-B [KO:K16198]
100698269  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100692625  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100694277  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
100689891  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
100702222  ccnh; cyclin-H [KO:K06634]
100693009  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100705288  anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
100698660  anapc2; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 2 [KO:K03349]
100695114  cdc27; cell division cycle protein 27 homolog isoform X3 [KO:K03350]
100695003  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
100699384  anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
100704900  cdc16; cell division cycle protein 16 homolog [KO:K03353]
100711935  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
100711746  cdc23; cell division cycle protein 23 homolog [KO:K03355]
100697992  anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
100703623  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
100699054  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
100695928  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
100711215  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
100696785  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
100706704  cdc20; cell division cycle protein 20 homolog [KO:K03363]
102082422  cell division cycle protein 20 homolog B isoform X1 [KO:K03363]
100691989  pttg1; securin [KO:K06635]
102078894  espl1; separin isoform X2 [KO:K02365] [EC:3.4.22.49]
100708270  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
100692924  structural maintenance of chromosomes protein 1B [KO:K06636]
100698498  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
100698455  double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
100710134  double-strand-break repair protein rad21 homolog [KO:K06670]
100705420  double-strand-break repair protein rad21 homolog [KO:K06670]
100703806  cohesin subunit SA-2 isoform X1 [KO:K06671]
100705321  cohesin subunit SA-1 isoform X3 [KO:K06671]
100692362  cohesin subunit SA-2 isoform X1 [KO:K06671]
100710355  cohesin subunit SA-2 [KO:K06671]
100690993  stag1; cohesin subunit SA-1 [KO:K06671]
100700822  atrx; transcriptional regulator ATRX isoform X2 [KO:K10779]
100690413  transcriptional regulator ATRX isoform X1 [KO:K10779]
100709583  ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
100691634  nipbl; nipped-B-like protein isoform X1 [KO:K06672]
100699860  nipped-B-like protein isoform X1 [KO:K06672]
100694478  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
100695091  MAU2 chromatid cohesion factor homolog [KO:K11266]
100710978  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
100710554  esco2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
100692908  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
100708754  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
100711254  wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
100712474  wings apart-like protein homolog [KO:K25163]
100701918  cdca5; sororin [KO:K17390]
100706117  aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
100701449  sgo1; shugoshin 1 isoform X1 [KO:K11580]
100710281  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100697538  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100705713  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100695673  ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
100709826  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100693611  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
100707563  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100694131  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
100695153  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X3 [KO:K11584]
109194260  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
100691363  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
100704962  knl1; kinetochore scaffold 1 [KO:K11542]
100698249  ttk; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
100697468  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
100709474  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
100698790  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
100706285  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
100691879  bub3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
100710499  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X5 [KO:K02178] [EC:2.7.11.1]
100710876  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
100691874  mad2l1bp; MAD2L1-binding protein isoform X1 [KO:K26093]
100694127  fizzy-related protein homolog isoform X1 [KO:K03364]
100696847  fizzy-related protein homolog [KO:K03364]
100704751  fbxo5; F-box only protein 5 [KO:K10292]
100703436  dual specificity protein phosphatase CDC14C isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100703039  dual specificity protein phosphatase CDC14AB isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100709887  cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100698988  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100703632  crebbp; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100709989  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100700725  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100706243  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
100712269  atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
100694314  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100697160  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100702587  p53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100703831  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
100705173  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100695767  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100707977  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100706093  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100706356  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100698715  growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
100707083  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100700462  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100702557  pcna; proliferating cell nuclear antigen [KO:K04802]
100707719  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100708289  chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
Reference
PMID:7908906
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D-type cyclin-binding regions of proliferating cell nuclear antigen.
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PMID:17568790
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CDC25 phosphatases in cancer cells: key players? Good targets?
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Nat Rev Cancer 7:495-507 (2007)
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PMID:9832503
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Transcriptional regulation of the cyclin D1 gene at a glance.
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CDK inhibitors: positive and negative regulators of G1-phase progression.
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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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PMID:12925736
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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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Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
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PMID:15838523
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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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Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
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Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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Reference
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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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Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity.
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Reference
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  Title
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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Reference
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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
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  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)
DOI:10.1073/pnas.95.12.6733
Reference
PMID:26650195
  Authors
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)
DOI:10.1007/s00018-015-2096-7
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
onl03030  DNA replication
onl04010  MAPK signaling pathway
onl04120  Ubiquitin mediated proteolysis
onl04210  Apoptosis
KO pathway
ko04110   
LinkDB

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