KEGG   PATHWAY: clum04110
Entry
clum04110                   Pathway                                
Name
Cell cycle - Cyclopterus lumpus (lumpfish)
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
clum04110  Cell cycle
clum04110

Other DBs
GO: 0000278
Organism
Cyclopterus lumpus (lumpfish) [GN:clum]
Gene
117725138  e2f2; transcription factor E2F2 isoform X1 [KO:K09389]
117725189  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
117725323  [KO:K06067] [EC:3.5.1.98]
117725352  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
117725426  [KO:K04402]
117725992  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
117726081  smc3; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 3 [KO:K06669]
117726348  ccnd2b; G1/S-specific cyclin-D2b isoform X1 [KO:K10151]
117726468  orc5; origin recognition complex subunit 5 [KO:K02607]
117726546  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
117727017  ppp2r5cb; protein phosphatase 2, regulatory subunit B', gamma b isoform X1 [KO:K11584]
117727087  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
117727104  knl1; uncharacterized protein knl1 isoform X1 [KO:K11542]
117727119  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
117727294  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
117727345  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
117727370  [KO:K13377]
117727592  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
117727947  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
117728074  ttk; dual specificity protein kinase Ttk isoform X1 [KO:K08866] [EC:2.7.12.1]
117728179  [KO:K16197]
117728311  tgfb2; LOW QUALITY PROTEIN: transforming growth factor beta-2 proprotein [KO:K13376]
117728634  [KO:K23605]
117728654  [KO:K21770]
117728784  cdkn1ca; cyclin-dependent kinase inhibitor 1Ca [KO:K09993]
117728839  [KO:K21770]
117729618  cdc14ab; dual specificity protein phosphatase CDC14AB isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117729733  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
117729771  orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
117729802  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
117730054  [KO:K04402]
117730066  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
117730094  [KO:K03364]
117730108  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
117730433  [KO:K16197]
117730559  rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
117730594  cdk4; LOW QUALITY PROTEIN: cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
117730674  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
117730883  espl1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
117731055  mcm2; DNA replication licensing factor MCM2 isoform X1 [KO:K02540] [EC:5.6.2.3]
117731143  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
117731176  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
117731737  cdkn2a/b; cyclin-dependent kinase inhibitor 2A [KO:K04685]
117731779  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
117731807  ticrr; treslin isoform X1 [KO:K26117]
117731813  smc1b; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
117731816  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
117731879  smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605]
117732096  ccnd2a; G1/S-specific cyclin-D2a isoform X1 [KO:K10151]
117732133  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
117732247  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
117732262  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
117732402  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
117732532  e2f4; transcription factor E2F4 isoform X1 [KO:K04682]
117732710  [KO:K04503]
117732744  cdc6; cell division control protein 6 homolog [KO:K02213]
117732745  cdkn1cb; cyclin-dependent kinase inhibitor 1C [KO:K09993]
117732801  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
117733391  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
117733420  e2f1; transcription factor E2F1 [KO:K17454]
117733548  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
117733710  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
117733763  rad21l1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
117733991  [KO:K16197]
117734722  ccndx; cyclin Dx [KO:K10151]
117735137  ep300b; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117735162  crebbpb; CREB binding protein b [KO:K04498] [EC:2.3.1.48]
117735189  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117735190  cdc27; cell division cycle protein 27 homolog [KO:K03350]
117735274  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
117735544  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
117735638  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117736039  [KO:K04382] [EC:3.1.3.16]
117736095  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117736134  ccnh; cyclin-H [KO:K06634]
117736183  [KO:K04500]
117736424  [KO:K04501]
117736482  anapc7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
117736612  [KO:K03363]
117736657  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
117736700  pcna; proliferating cell nuclear antigen [KO:K04802]
117736817  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
117736873  cdc45; cell division control protein 45 homolog [KO:K06628]
117736875  gadd45ga; growth arrest and DNA-damage-inducible, gamma a isoform X1 [KO:K04402]
117736988  nipbla; nipped-B-like protein A isoform X1 [KO:K06672]
117737139  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
117737141  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
117737172  stag2b; cohesin subunit SA-2 [KO:K06671]
117737456  pttg1; securin [KO:K06635]
117737475  [KO:K06671]
117737528  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117737713  [KO:K04382] [EC:3.1.3.16]
117737765  mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
117737854  ccna2; cyclin-A2 [KO:K06627]
117737908  aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
117737955  mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
117738570  [KO:K06670]
117738587  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117738600  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117738760  [KO:K06067] [EC:3.5.1.98]
117738861  cdca5; sororin [KO:K17390]
117738886  [KO:K16197]
117739024  [KO:K06626]
117739532  e2f3; transcription factor E2F3 [KO:K06620]
117739546  sgo1; shugoshin 1 [KO:K11580]
117740108  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117740118  smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
117740198  [KO:K06672]
117740236  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
117740530  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
117740536  [KO:K04402]
117740539  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
117740880  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
117740939  skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
117740977  orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
117740985  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117741161  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 [KO:K06630]
117741227  tgfb1a; transforming growth factor, beta 1a isoform X1 [KO:K13375]
117741228  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117741262  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
117741471  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
117741719  ccnp; cyclin N-terminal domain-containing protein 2 [KO:K21770]
117741876  ywhag2; 14-3-3 protein gamma-1 [KO:K16198]
117741960  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
117742510  stag2a; cohesin subunit SA-2a isoform X1 [KO:K06671]
117742533  cdc23; cell division cycle protein 23 homolog [KO:K03355]
117742541  rb1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
117742585  pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
117742591  [KO:K06630]
117742791  ccna1; cyclin-A1 [KO:K06627]
117742883  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117743022  [KO:K10779]
117743043  skp1; S-phase kinase-associated protein 1 [KO:K03094]
117743135  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
117743221  chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
117743746  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
117743775  fbxo5; LOW QUALITY PROTEIN: F-box only protein 5 [KO:K10292]
117743822  wapla; wings apart-like protein homolog [KO:K25163]
117743846  mad2l1bp; MAD2L1-binding protein [KO:K26093]
117744089  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
117744214  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
117744461  cdt1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
117745136  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
117745283  [KO:K06620]
117745319  dbf4; protein DBF4 homolog A [KO:K06629]
117745359  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
117745531  [KO:K06670]
117745841  mtbp; mdm2-binding protein isoform X1 [KO:K26116]
117745927  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
117745948  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
117746197  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
117746732  [KO:K03364]
117746765  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
117746842  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
117746886  cdc20; cell division cycle protein 20 homolog [KO:K03363]
117746935  fzr1b; fizzy-related protein homolog isoform X1 [KO:K03364]
117747008  orc2; origin recognition complex subunit 2 [KO:K02604]
117747090  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117747594  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
117747693  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
117747715  tp53; cellular tumor antigen p53 [KO:K04451]
117748048  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
117748049  hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
117748180  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
117748337  [KO:K25163]
117748463  [KO:K04682]
117748516  anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
117748979  ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
117749026  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
117749096  dbf4b; uncharacterized protein dbf4b [KO:K06629]
117749160  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
117749214  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117749293  myca; transcriptional regulator Myc-A [KO:K04377]
117749370  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
117749841  [KO:K03347]
117750245  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117750541  si:ch211-269e2.1; cohesin subunit SA-2 isoform X1 [KO:K06671]
117750553  [KO:K04683]
117750994  cdc16; cell division cycle protein 16 homolog [KO:K03353]
117751082  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
117751090  stag1a; cohesin subunit SA-1a [KO:K06671]
117751191  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X1 [KO:K11584]
117751254  [KO:K16197]
117751271  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
117751419  [KO:K04681]
117751643  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117751658  orc3; origin recognition complex subunit 3 [KO:K02605]
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
  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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  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.
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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)
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Reference
PMID:9832503
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  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
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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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Reference
PMID:10385618
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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
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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
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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.
  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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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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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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Reference
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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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Nat Rev Mol Cell Biol 8:379-93 (2007)
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Reference
PMID:12573239
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  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
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  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)
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Reference
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  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
clum03030  DNA replication
clum04010  MAPK signaling pathway
clum04120  Ubiquitin mediated proteolysis
clum04210  Apoptosis
KO pathway
ko04110   

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