KEGG   PATHWAY: smau04110
Entry
smau04110                   Pathway                                
Name
Cell cycle - Scophthalmus maximus (turbot)
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
smau04110  Cell cycle
smau04110

Other DBs
GO: 0000278
Organism
Scophthalmus maximus (turbot) [GN:smau]
Gene
118302431  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
118314882  G1/S-specific cyclin-D1-like [KO:K04503]
118315746  ccnd2a; G1/S-specific cyclin-D2a isoform X1 [KO:K10151]
118288503  G1/S-specific cyclin-D2 [KO:K10151]
118288636  ccndx; cyclin Dx [KO:K10151]
118309273  ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
118309388  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
118288690  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
118291934  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
118300850  rb1; retinoblastoma-associated protein [KO:K06618]
118302568  retinoblastoma-like protein 2 isoform X1 [KO:K04681]
118308753  rbl1; retinoblastoma-like protein 1 [KO:K04681]
118284470  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
118311091  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
118286006  histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
118290620  LOW QUALITY PROTEIN: histone deacetylase 2-like [KO:K06067] [EC:3.5.1.98]
118317237  e2f1; transcription factor E2F1 [KO:K17454]
118286352  e2f2; transcription factor E2F2 isoform X1 [KO:K09389]
118310914  e2f3; transcription factor E2F3 isoform X1 [KO:K06620]
118305885  transcription factor E2F3 [KO:K06620]
118315745  e2f4; transcription factor E2F4 [KO:K04682]
118311241  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
118301810  transcription factor E2F4 isoform X2 [KO:K04682]
118320482  tfdp1a; transcription factor Dp-1a [KO:K04683]
118320556  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118299716  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
118318986  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
118285006  tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
118289917  transforming growth factor beta-3 proprotein [KO:K13377]
118286691  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
118313368  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118302389  mothers against decapentaplegic homolog 3 [KO:K23605]
118315953  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
118310429  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
118284760  smad4a; mothers against decapentaplegic homolog 4a isoform X1 [KO:K04501]
118314169  mothers against decapentaplegic homolog 4 [KO:K04501]
118285476  mothers against decapentaplegic homolog 4-like [KO:K04501]
118287792  myca; transcriptional regulator Myc-A isoform X1 [KO:K04377]
118311397  transcriptional regulator Myc-B-like isoform X1 [KO:K04377]
118308779  mych; myelocytomatosis oncogene homolog isoform X1 [KO:K04377]
118316987  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
118312542  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
118317645  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
118312950  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
118290624  cyclin-dependent kinase inhibitor 1B [KO:K06624]
118314970  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
118315943  cyclin-dependent kinase inhibitor 1C-like [KO:K09993]
118302446  cdkn1ca; cyclin-dependent kinase inhibitor 1Ca [KO:K09993]
118319569  cdkn1d; cyclin-dependent kinase inhibitor 1D isoform X1 [KO:K06625]
118309289  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
118284671  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
118291742  G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
118302443  ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
118309643  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
118300137  skp1; S-phase kinase-associated protein 1 [KO:K03094]
118291306  cullin-1 [KO:K03347]
118289065  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
118284506  skp2; S-phase kinase-associated protein 2 [KO:K03875]
118300816  ccna1; cyclin-A1 [KO:K06627]
118319733  ccna2; cyclin-A2 [KO:K06627]
118313194  cdc6; cell division control protein 6 homolog [KO:K02213]
118284263  cdt1; DNA replication factor Cdt1 [KO:K10727]
118318123  orc1; origin recognition complex subunit 1 [KO:K02603]
118311774  orc2; origin recognition complex subunit 2 [KO:K02604]
118286238  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
118299102  orc4; origin recognition complex subunit 4 [KO:K02606]
118286090  orc5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
118308759  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
118290473  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
118311047  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
118288554  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
118311760  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
118319756  mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
118314526  cdc45; cell division control protein 45 homolog [KO:K06628]
118315780  ticrr; treslin isoform X1 [KO:K26117]
118313244  mdm2-binding protein [KO:K26116]
118311731  cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
118287889  dbf4b; uncharacterized protein dbf4b [KO:K06629]
118300754  dbf4; protein DBF4 homolog A [KO:K06629]
118283885  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
118284987  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
118299287  cyclin N-terminal domain-containing protein 2 [KO:K21770]
118284622  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
118285811  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
118317574  14-3-3 protein beta/alpha-1 [KO:K16197]
118286027  14-3-3 protein beta/alpha-B [KO:K16197]
118291852  14-3-3 protein beta/alpha-B [KO:K16197]
118299036  14-3-3 protein zeta/delta [KO:K16197]
118308919  ywhaba; 14-3-3 protein beta/alpha-A [KO:K16197]
118299666  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 [KO:K06630]
118300622  14-3-3 protein epsilon [KO:K06630]
118301362  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
118298949  ywhag2; 14-3-3 protein gamma-B [KO:K16198]
118312290  plk1; serine/threonine-protein kinase PLK1 isoform X1 [KO:K06631] [EC:2.7.11.21]
118315991  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
118315573  wee2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
118287655  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
118313906  ccnh; cyclin-H [KO:K06634]
118314313  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
118283365  anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
118289090  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
118288893  cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
118317812  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
118314292  anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
118282957  cdc16; cell division cycle protein 16 homolog [KO:K03353]
118313702  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
118301162  cdc23; cell division cycle protein 23 homolog [KO:K03355]
118285286  anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
118313274  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
118284540  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
118315732  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
118299702  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
118287108  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
118311145  cdc20; cell division cycle protein 20 homolog [KO:K03363]
118313573  cell division cycle protein 20 homolog B-like [KO:K03363]
118309718  espl1; separin [KO:K02365] [EC:3.4.22.49]
118315604  smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
118316291  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
118313113  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
118308418  double-strand-break repair protein rad21 homolog A [KO:K06670]
118316671  rad21l1; double-strand-break repair protein rad21-like protein 1 isoform X1 [KO:K06670]
118319489  stag2b; cohesin subunit SA-2 [KO:K06671]
118301557  stag2a; cohesin subunit SA-2a isoform X1 [KO:K06671]
118319754  cohesin subunit SA-2 [KO:K06671]
118285734  stag1a; cohesin subunit SA-1a [KO:K06671]
118320399  si:ch211-269e2.1; cohesin subunit SA-2 isoform X1 [KO:K06671]
118300138  transcriptional regulator ATRX-like isoform X2 [KO:K10779]
118319330  atrx; transcriptional regulator ATRX [KO:K10779]
118314925  ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
118284591  nipped-B-like protein isoform X1 [KO:K06672]
118313918  nipbla; nipped-B-like protein A isoform X1 [KO:K06672]
118318293  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
118284690  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
118290222  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
118300042  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
118311949  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
118283743  wapla; wings apart-like protein homolog [KO:K25163]
118287183  wings apart-like protein homolog [KO:K25163]
118292068  cdca5; sororin [KO:K17390]
118319840  aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
118292121  sgo1; shugoshin 1 [KO:K11580]
118301163  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118319860  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
118313857  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
118299655  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
118300163  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
118284148  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
118290076  ppp2r5cb; protein phosphatase 2, regulatory subunit B', gamma b isoform X1 [KO:K11584]
118290079  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
118285914  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X5 [KO:K11584]
118286095  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118314479  ndc80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
118299336  ttk; dual specificity protein kinase Ttk isoform X2 [KO:K08866] [EC:2.7.12.1]
118312683  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
118300848  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
118316593  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
118286281  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
118287766  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
118290011  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
118286013  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
118283507  MAD2L1-binding protein isoform X1 [KO:K26093]
118310765  fzr1b; fizzy-related protein homolog [KO:K03364]
118311304  fizzy-related protein homolog [KO:K03364]
118318611  fizzy-related protein homolog isoform X2 [KO:K03364]
118284134  fbxo5; F-box only protein 5 [KO:K10292]
118311530  dual specificity protein phosphatase CDC14AB-like isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
118317777  cdc14ab; dual specificity protein phosphatase CDC14AB isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
118313910  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
118288286  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
118312150  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
118289066  ep300b; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
118287257  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
118290862  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
118286109  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
118295539  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
118289952  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X3 [KO:K06643] [EC:2.3.2.27]
118320602  tp53; cellular tumor antigen p53 [KO:K04451]
118311308  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a isoform X1 [KO:K04402]
118317955  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
118318717  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
118285387  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
124849746  growth arrest and DNA damage-inducible protein GADD45 gamma-like [KO:K04402]
118286359  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
118314489  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
118314249  pcna; proliferating cell nuclear antigen [KO:K04802]
118301186  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
118314379  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [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)
Reference
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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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
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Pocket proteins and cell cycle control.
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Oncogene 24:2796-809 (2005)
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Reference
PMID:17568790
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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)
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Reference
PMID:9832503
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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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PMID:19020303
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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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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)
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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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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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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
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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
  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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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
  Authors
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
smau03030  DNA replication
smau04010  MAPK signaling pathway
smau04120  Ubiquitin mediated proteolysis
smau04210  Apoptosis
KO pathway
ko04110   
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