KEGG   PATHWAY: tben04110
Entry
tben04110                   Pathway                                
Name
Cell cycle - Trematomus bernacchii (emerald rockcod)
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
tben04110  Cell cycle
tben04110

Other DBs
GO: 0000278
Organism
Trematomus bernacchii (emerald rockcod) [GN:tben]
Gene
117468756  [KO:K10779]
117468820  stag2a; cohesin subunit SA-2a isoform X1 [KO:K06671]
117468925  ywhag2; 14-3-3 protein gamma-2 [KO:K16198]
117468953  rb1; retinoblastoma-associated protein [KO:K06618]
117469109  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
117469144  cdc27; LOW QUALITY PROTEIN: cell division cycle protein 27 homolog [KO:K03350]
117469155  e2f2; transcription factor E2F2 [KO:K09389]
117469438  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
117469787  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
117469797  [KO:K03357]
117469839  [KO:K03357]
117470104  atm; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
117470186  ccnp; cyclin N-terminal domain-containing protein 2 isoform X1 [KO:K21770]
117470339  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117470359  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
117470654  [KO:K04501]
117470704  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
117471004  [KO:K06643] [EC:2.3.2.27]
117471062  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
117471175  [KO:K23605]
117471236  [KO:K04682]
117471526  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117471643  cdkn1ca; cyclin-dependent kinase inhibitor 1Ca [KO:K09993]
117472040  [KO:K04377]
117472241  [KO:K21770]
117472243  [KO:K21770]
117472282  [KO:K06643] [EC:2.3.2.27]
117472440  cdc45; cell division control protein 45 homolog [KO:K06628]
117472515  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117472539  nipbla; nipped-B-like protein A isoform X1 [KO:K06672]
117472627  ccnh; cyclin-H [KO:K06634]
117472774  pcna; proliferating cell nuclear antigen [KO:K04802]
117472912  [KO:K04501]
117472958  [KO:K06067] [EC:3.5.1.98]
117472996  [KO:K04382] [EC:3.1.3.16]
117473112  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
117473119  [KO:K03363]
117473245  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
117473251  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
117473612  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
117473814  dbf4b; uncharacterized protein dbf4b isoform X1 [KO:K06629]
117473829  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
117473931  [KO:K16197]
117474074  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
117474494  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
117474575  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117474651  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
117474972  stag2b; cohesin subunit SA-2 [KO:K06671]
117475080  [KO:K04382] [EC:3.1.3.16]
117475282  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
117475413  cdt1; DNA replication factor Cdt1 [KO:K10727]
117475725  [KO:K11584]
117475970  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
117476245  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
117476375  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117476476  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X1 [KO:K11584]
117476804  [KO:K06672]
117476827  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
117477027  [KO:K06630]
117477928  [KO:K06670]
117477931  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
117477949  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117477965  [KO:K16197]
117478056  [KO:K11580]
117478094  [KO:K06626]
117478197  cdca5; sororin [KO:K17390]
117478734  [KO:K05868]
117478736  [KO:K05868]
117478778  skp2; LOW QUALITY PROTEIN: S-phase kinase-associated protein 2 [KO:K03875]
117478883  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117478900  [KO:K05868]
117478959  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
117478976  [KO:K04402]
117479211  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117479494  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
117479510  [KO:K16197]
117480026  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
117480044  ttk; dual specificity protein kinase Ttk [KO:K08866] [EC:2.7.12.1]
117480082  dbf4; LOW QUALITY PROTEIN: protein DBF4 homolog A [KO:K06629]
117480123  mtbp; mdm2-binding protein isoform X1 [KO:K26116]
117480154  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
117480401  [KO:K06670]
117480415  [KO:K06620]
117480729  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
117480770  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
117481007  [KO:K04683]
117481031  cdc16; cell division cycle protein 16 homolog [KO:K03353]
117481110  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117481153  si:ch211-269e2.1; cohesin subunit SA-2 isoform X1 [KO:K06671]
117481639  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
117481851  cdc6; cell division control protein 6 homolog [KO:K02213]
117482168  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117482315  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
117482339  mad1l1; LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
117482687  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
117482806  [KO:K06620]
117482883  [KO:K06067] [EC:3.5.1.98]
117483300  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
117483302  [KO:K06624]
117483594  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
117484101  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
117484558  rad21l1; LOW QUALITY PROTEIN: double-strand-break repair protein rad21-like protein 1 [KO:K06670]
117484765  [KO:K04500]
117484779  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
117484991  [KO:K10151]
117485087  orc5; origin recognition complex subunit 5 [KO:K02607]
117485264  ccna2; cyclin-A2 [KO:K06627]
117486231  orc4; origin recognition complex subunit 4 [KO:K02606]
117486377  [KO:K02178] [EC:2.7.11.1]
117486404  [KO:K04498] [EC:2.3.1.48]
117486411  [KO:K04498] [EC:2.3.1.48]
117486569  rbl1; retinoblastoma-like protein 1 [KO:K04681]
117486917  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
117487016  knl1; kinetochore scaffold 1 isoform X1 [KO:K11542]
117487064  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
117487640  pttg1; securin [KO:K06635]
117487965  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
117488086  tp53; cellular tumor antigen p53 [KO:K04451]
117488277  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
117488302  cdc20; cell division cycle protein 20 homolog [KO:K03363]
117488327  orc2; origin recognition complex subunit 2 [KO:K02604]
117488393  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
117488435  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
117488651  [KO:K03364]
117488821  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117488935  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
117488985  [KO:K03364]
117489024  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
117489633  espl1; separin [KO:K02365] [EC:3.4.22.49]
117489719  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
117489894  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
117489963  [KO:K11479] [EC:2.7.11.1]
117489997  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
117490010  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
117490066  [KO:K06630]
117490104  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
117490113  [KO:K06671]
117490151  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
117490366  [KO:K11479] [EC:2.7.11.1]
117490390  pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
117490479  cdc23; cell division cycle protein 23 homolog [KO:K03355]
117490538  ccna1; cyclin-A1 [KO:K06627]
117490736  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117490737  skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
117491000  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
117491130  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
117491133  orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
117491260  [KO:K04503]
117491403  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
117491556  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117491667  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
117491752  e2f4; transcription factor E2F4 [KO:K04682]
117491762  ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
117491872  ccnd2a; G1/S-specific cyclin-D2a isoform X1 [KO:K10151]
117492467  [KO:K04498] [EC:2.3.1.48]
117492468  anapc2; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 2 [KO:K03349]
117492771  ep300b; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117492884  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117493088  ccndx; cyclin Dx [KO:K10151]
117493170  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117493459  [KO:K13377]
117493804  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
117493868  stag1a; cohesin subunit SA-1a isoform X1 [KO:K06671]
117493995  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
117494202  zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
117494349  myca; transcriptional regulator Myc-A [KO:K04377]
117494423  e2f1; transcription factor E2F1 [KO:K17454]
117494431  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
117494619  [KO:K21771]
117495641  [KO:K03364]
117495687  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
117495941  [KO:K03347]
117496225  [KO:K04402]
117496443  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
117496472  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
117496701  [KO:K04681]
117497204  smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
117497304  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
117497323  ticrr; LOW QUALITY PROTEIN: treslin [KO:K26117]
117497386  [KO:K16197]
117497428  [KO:K09993]
117497461  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
117497650  [KO:K25163]
117497777  cdkn2c; cyclin-dependent kinase 4 inhibitor C isoform X1 [KO:K06622]
117497834  cdc14ab; dual specificity protein phosphatase CDC14AB [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117497859  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
117497879  ywhaba; 14-3-3 protein beta/alpha-A [KO:K16197]
117497961  [KO:K11405] [EC:3.5.1.98]
117498381  ppp2r5cb; protein phosphatase 2, regulatory subunit B', gamma b isoform X1 [KO:K11584]
117498551  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
117499380  fbxo5; F-box only protein 5 [KO:K10292]
117499642  wapla; wings apart-like protein homolog isoform X1 [KO:K25163]
117499681  mad2l1bp; MAD2L1-binding protein [KO:K26093]
117499784  anapc1; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 1 [KO:K03348]
117500142  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
Reference
PMID:7908906
  Authors
Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
  Journal
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.
  Journal
Cell 75:779-90 (1993)
DOI:10.1016/0092-8674(93)90497-E
Reference
PMID:16936746
  Authors
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.
  Journal
Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
  Authors
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?
  Journal
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.
  Journal
Genes Dev 12:3499-511 (1998)
DOI:10.1101/gad.12.22.3499
Reference
PMID:19020303
  Authors
Klein EA, Assoian RK
  Title
Transcriptional regulation of the cyclin D1 gene at a glance.
  Journal
J Cell Sci 121:3853-7 (2008)
DOI:10.1242/jcs.039131
Reference
PMID:10385618
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
  Journal
Genes Dev 13:1501-12 (1999)
DOI:10.1101/gad.13.12.1501
Reference
PMID:12809600
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:12925736
  Authors
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.
  Journal
Proc Natl Acad Sci U S A 100:10231-6 (2003)
DOI:10.1073/pnas.1831009100
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.
  Journal
Cardiovasc Res 69:198-206 (2006)
DOI:10.1016/j.cardiores.2005.08.020
Reference
PMID:15838523
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11099028
  Authors
Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
  Journal
Nature 408:307-10 (2000)
DOI:10.1038/35042675
Reference
PMID:7973727
  Authors
Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
  Title
Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
  Journal
Science 266:1376-80 (1994)
DOI:10.1126/science.7973727
Reference
PMID:9889196
  Authors
Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K
  Title
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
  Journal
EMBO J 18:396-410 (1999)
DOI:10.1093/emboj/18.2.396
Reference
PMID:17018296
  Authors
Sheu YJ, Stillman B
  Title
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
  Journal
Mol Cell 24:101-13 (2006)
DOI:10.1016/j.molcel.2006.07.033
Reference
PMID:9029154
  Authors
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.
  Journal
EMBO J 16:343-54 (1997)
DOI:10.1093/emboj/16.2.343
Reference
PMID:15876871
  Authors
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)
DOI:10.4161/cc.4.4.1607
Reference
PMID:17426725
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
  Journal
Nat Rev Mol Cell Biol 8:379-93 (2007)
DOI:10.1038/nrm2163
Reference
PMID:12573239
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
DOI:10.1016/S0960-9822(03)00039-3
Reference
PMID:15568976
  Authors
Stegmeier F, Amon A
  Title
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
  Journal
Annu Rev Genet 38:203-32 (2004)
DOI:10.1146/annurev.genet.38.072902.093051
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
tben03030  DNA replication
tben04010  MAPK signaling pathway
tben04120  Ubiquitin mediated proteolysis
tben04210  Apoptosis
KO pathway
ko04110   

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