KEGG   PATHWAY: pov04110
Entry
pov04110                    Pathway                                
Name
Cell cycle - Paralichthys olivaceus (Japanese flounder)
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
pov04110  Cell cycle
pov04110

Other DBs
GO: 0000278
Organism
Paralichthys olivaceus (Japanese flounder) [GN:pov]
Gene
109625110  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109642994  G1/S-specific cyclin-D1-like isoform X1 [KO:K04503]
109632688  G1/S-specific cyclin-D2-like [KO:K10151]
109623974  G1/S-specific cyclin-D2-like [KO:K10151]
109629233  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
109629352  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
109634060  cyclin-dependent kinase 4-like [KO:K02091] [EC:2.7.11.22]
109631907  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
109628702  rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
109624795  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K04681]
109645359  rbl1; retinoblastoma-like protein 1 [KO:K04681]
109646631  retinoblastoma-like protein 2 [KO:K16332]
109626307  tyrosine-protein kinase ABL1-like isoform X1 [KO:K06619] [EC:2.7.10.2]
109632588  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
109631851  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
109628055  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
109630589  transcription factor E2F1-like [KO:K17454]
109628156  e2f2; transcription factor E2F2 [KO:K09389]
109631749  transcription factor E2F3-like isoform X1 [KO:K06620]
109632164  e2f3; transcription factor E2F3 [KO:K06620]
109637755  transcription factor E2F5-like [KO:K04682]
109624347  e2f4; transcription factor E2F4 [KO:K04682]
109636836  transcription factor E2F5-like [KO:K04682]
109631414  tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
109631323  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109630415  transforming growth factor beta-1-like [KO:K13375]
109642431  transforming growth factor beta-2-like [KO:K13376]
109631969  tgfb2; transforming growth factor beta-2 [KO:K13376]
109628154  tgfb3; transforming growth factor beta-3 [KO:K13377]
109636158  transforming growth factor beta-3-like [KO:K13377]
109633657  mothers against decapentaplegic homolog 2-like [KO:K04500]
109626315  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
109637282  mothers against decapentaplegic homolog 3 [KO:K23605]
109624649  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
109642417  mothers against decapentaplegic homolog 4 [KO:K04501]
109626289  mothers against decapentaplegic homolog 4-like [KO:K04501]
109641002  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
109643214  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
109629885  myc; myc proto-oncogene protein [KO:K04377]
109642921  transcriptional regulator Myc-2-like [KO:K04377]
109630484  zbtb17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
109638248  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
109627635  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
109632735  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
109624669  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
109623951  cyclin-dependent kinase inhibitor 1C-like [KO:K09993]
109637230  cyclin-dependent kinase inhibitor 1-like [KO:K09993]
109629024  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1-like [KO:K06625]
109632907  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
109640569  G1/S-specific cyclin-E2-like [KO:K06626]
109625045  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
109645281  G1/S-specific cyclin-E2-like [KO:K06626]
109629344  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
109635809  skp1; S-phase kinase-associated protein 1 [KO:K03094]
109645364  cul1; cullin-1 [KO:K03347]
109643626  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109647460  skp2; S-phase kinase-associated protein 2 [KO:K03875]
109640437  ccna2; cyclin-A2 [KO:K06627]
109635759  ccna1; cyclin-A1 isoform X1 [KO:K06627]
109641852  cdc6; cell division control protein 6 homolog [KO:K02213]
109639883  cdt1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
109643780  orc1; origin recognition complex subunit 1 [KO:K02603]
109644328  orc2; origin recognition complex subunit 2 [KO:K02604]
109627791  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
109639036  orc4; origin recognition complex subunit 4 [KO:K02606]
109642846  orc5; origin recognition complex subunit 5 [KO:K02607]
109643130  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
109632580  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
109646138  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
109647511  DNA replication licensing factor mcm5-like [KO:K02209] [EC:5.6.2.3]
109645694  DNA replication licensing factor mcm5-like [KO:K02209] [EC:5.6.2.3]
109646575  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
109646121  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
109637017  cdc45; cell division control protein 45 homolog [KO:K06628]
109624536  ticrr; treslin [KO:K26117]
109631954  mtbp; mdm2-binding protein [KO:K26116]
109639327  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
109633450  dbf4; protein DBF4 homolog A [KO:K06629]
109627061  histone-lysine N-methyltransferase 2D-like [KO:K06629]
109639858  cyclin-dependent kinase 1-like [KO:K02087] [EC:2.7.11.22 2.7.11.23]
109640910  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
109647535  G2/mitotic-specific cyclin-B2-like [KO:K21770]
109634457  G2/mitotic-specific cyclin-B2-like isoform X1 [KO:K21770]
109640808  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
109636485  M-phase inducer phosphatase 1-like [KO:K05866] [EC:3.1.3.48]
109632163  14-3-3 protein zeta-like [KO:K16197]
109628012  ywhaq; 14-3-3 protein theta isoform X1 [KO:K16197]
109640946  14-3-3 protein beta/alpha-1 [KO:K16197]
109635138  14-3-3 protein beta/alpha-1-like [KO:K16197]
109638824  14-3-3 protein eta-like [KO:K16197]
109634553  ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109635855  14-3-3 protein epsilon-like [KO:K06630]
109628728  14-3-3 protein gamma-1 [KO:K16198]
109630359  14-3-3 protein gamma-B [KO:K16198]
109646908  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
109624555  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
109639888  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
109642806  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
109633795  ccnh; cyclin-H [KO:K06634]
109638069  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
109634767  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
109646800  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
109643343  cdc27; cell division cycle protein 27 homolog [KO:K03350]
109625520  anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
109633883  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
109637998  cdc16; cell division cycle protein 16 homolog [KO:K03353]
109633748  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
109628623  cdc23; cell division cycle protein 23 homolog [KO:K03355]
109623637  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
109627312  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
109646158  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
109624685  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
109634552  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
109627105  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
109640100  cdc20; cell division cycle protein 20 homolog [KO:K03363]
109637174  cdc20b; cell division cycle protein 20 homolog B isoform X1 [KO:K03363]
109626412  securin-like [KO:K06635]
109628965  espl1; separin [KO:K02365] [EC:3.4.22.49]
109630824  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
109624005  structural maintenance of chromosomes protein 1B-like isoform X1 [KO:K06636]
109627587  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
109632191  double-strand-break repair protein rad21 homolog [KO:K06670]
109639139  double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
109642095  double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
109628708  cohesin subunit SA-2-like isoform X1 [KO:K06671]
109636433  stag1; cohesin subunit SA-1 [KO:K06671]
109626259  cohesin subunit SA-1-like [KO:K06671]
109637927  cohesin subunit SA-2-like [KO:K06671]
109646244  cohesin subunit SA-2-like [KO:K06671]
109628644  transcriptional regulator ATRX-like isoform X1 [KO:K10779]
109638410  transcriptional regulator ATRX-like [KO:K10779]
109644201  transcriptional regulator ATRX-like [KO:K10779]
109624354  ATP-dependent DNA helicase DDX11-like isoform X1 [KO:K11273] [EC:5.6.2.7]
109626329  nipped-B-like protein isoform X1 [KO:K06672]
109638137  nipbl; nipped-B-like protein isoform X1 [KO:K06672]
109625781  MAU2 chromatid cohesion factor homolog [KO:K11266]
109636982  MAU2 chromatid cohesion factor homolog [KO:K11266]
109643410  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
109643234  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
109635725  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
109637820  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
109634973  wapl; wings apart-like protein homolog [KO:K25163]
109643975  wings apart-like protein homolog [KO:K25163]
109639995  cdca5; sororin [KO:K17390]
109632179  aurora kinase B-like [KO:K11479] [EC:2.7.11.1]
109631809  sgo1; shugoshin 1 isoform X1 [KO:K11580]
109643848  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
109628717  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109630286  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109646534  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform-like [KO:K11584]
109628107  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
109632499  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform-like isoform X1 [KO:K11584]
109643033  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
109636067  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
109634925  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
109638034  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
109635971  knl1; protein CASC5 [KO:K11542]
109632253  ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
109639600  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
109637710  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
109630511  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
109628147  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
109626583  bub3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
109646401  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
109633499  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
109629664  mad2l1bp; MAD2L1-binding protein [KO:K26093]
109645638  fizzy-related protein homolog [KO:K03364]
109638664  fizzy-related protein homolog [KO:K03364]
109625276  fizzy-related protein homolog isoform X1 [KO:K03364]
109629454  fbxo5; F-box only protein 5 [KO:K10292]
109643886  LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14AB-like [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109637114  dual specificity protein phosphatase CDC14A-like isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109646188  dual specificity protein phosphatase CDC14AB [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109627429  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109643520  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
109626906  histone acetyltransferase p300-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109638720  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109629764  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
109640857  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
109634588  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
109643735  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
109634900  cellular tumor antigen p53-like isoform X1 [KO:K04451]
109644407  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109637499  growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402]
109636370  growth arrest and DNA damage-inducible protein GADD45 beta-like isoform X1 [KO:K04402]
109639301  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109625451  growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402]
109643194  growth arrest and DNA damage-inducible protein GADD45 gamma-like [KO:K04402]
109637157  pcna; proliferating cell nuclear antigen [KO:K04802]
109628292  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
109645723  serine/threonine-protein kinase Chk2-like [KO:K06641] [EC:2.7.11.1]
Reference
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Oncogene 25:5263-7 (2006)
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PMID:15838516
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Pocket proteins and cell cycle control.
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Oncogene 24:2796-809 (2005)
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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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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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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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CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
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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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PMID:12925736
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Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, Hatakeyama S, Nakayama K, Nakayama KI
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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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PMID:16212951
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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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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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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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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
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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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Lolli G, Johnson LN
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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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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
  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
pov03030  DNA replication
pov04010  MAPK signaling pathway
pov04120  Ubiquitin mediated proteolysis
pov04210  Apoptosis
KO pathway
ko04110   
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