KEGG   PATHWAY: eee04110
Entry
eee04110                    Pathway                                
Name
Cell cycle - Electrophorus electricus (electric eel)
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
eee04110  Cell cycle
eee04110

Other DBs
GO: 0000278
Organism
Electrophorus electricus (electric eel) [GN:eee]
Gene
113567673  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
113567946  [KO:K04501]
113568101  [KO:K04685]
113568152  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
113568191  [KO:K10779]
113568595  [KO:K10151]
113569220  orc5; origin recognition complex subunit 5 [KO:K02607]
113569662  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
113569689  [KO:K11584]
113569723  ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
113569990  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
113570086  [KO:K03364]
113570174  tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
113570444  orc1; origin recognition complex subunit 1 [KO:K02603]
113570531  ywhaq; 14-3-3 protein theta [KO:K16197]
113570678  mtbp; mdm2-binding protein isoform X1 [KO:K26116]
113570745  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
113570762  ccna2; cyclin-A2 [KO:K06627]
113570887  ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
113570995  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
113571038  cdc45; cell division control protein 45 homolog [KO:K06628]
113571196  [KO:K04501]
113571360  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
113571418  [KO:K06671]
113571806  ticrr; treslin [KO:K26117]
113572001  [KO:K09389]
113572097  cdkn2c; cyclin-dependent kinase 4 inhibitor C isoform X1 [KO:K06622]
113572189  ccna1; cyclin-A1 [KO:K06627]
113572191  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
113572459  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
113572476  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
113572522  [KO:K06624]
113572706  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
113572719  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
113572732  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
113572783  anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
113572864  ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
113572896  ccnh; cyclin-H isoform X1 [KO:K06634]
113572926  chek2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
113572986  [KO:K11584]
113573139  rbl2; retinoblastoma-like protein 2 [KO:K16332]
113573267  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
113573295  smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
113573306  nipbl; nipped-B-like protein isoform X1 [KO:K06672]
113573544  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
113573558  [KO:K06625]
113573574  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
113573626  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
113573654  [KO:K09993]
113573801  [KO:K13375]
113573843  [KO:K04377]
113574003  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
113574008  rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
113574086  [KO:K23605]
113574196  skp2; S-phase kinase-associated protein 2 [KO:K03875]
113574213  [KO:K16197]
113574226  rbl1; retinoblastoma-like protein 1 [KO:K04681]
113574475  cdc14a; dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
113574737  [KO:K09392]
113574829  ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
113574943  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
113574949  knl1; kinetochore scaffold 1 isoform X1 [KO:K11542]
113574991  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
113575130  [KO:K16198]
113575152  fzr1; fizzy-related protein homolog [KO:K03364]
113575526  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
113575643  [KO:K16197]
113575666  esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
113575702  cdt1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
113575732  ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
113575830  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
113575991  espl1; separin [KO:K02365] [EC:3.4.22.49]
113576129  [KO:K06671]
113576465  [KO:K06671]
113576577  hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
113576788  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
113576838  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
113577034  dbf4; protein DBF4 homolog A [KO:K06629]
113577352  [KO:K04451]
113577362  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
113577513  tfdp1; transcription factor Dp-1 [KO:K04683]
113577545  [KO:K16198]
113577926  [KO:K06632] [EC:2.7.11.1]
113578036  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
113578037  skp1; S-phase kinase-associated protein 1 [KO:K03094]
113578084  [KO:K10151]
113578407  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
113578445  [KO:K06670]
113578561  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
113578681  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
113578771  [KO:K06670]
113578772  [KO:K16197]
113578819  [KO:K06670]
113578840  anapc11; anaphase-promoting complex subunit 11 isoform X1 [KO:K03358]
113578872  [KO:K04402]
113578873  [KO:K04402]
113578962  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
113579280  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
113579285  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
113579551  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
113579598  [KO:K03456]
113579698  [KO:K09993]
113579837  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
113579860  [KO:K16197]
113579862  [KO:K04402]
113579948  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
113580026  trip13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
113580094  sgo1; shugoshin 1 isoform X1 [KO:K11580]
113580168  zbtb17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
113580680  [KO:K04498] [EC:2.3.1.48]
113580689  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
113580786  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
113580908  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
113581069  mcm3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
113581589  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
113581635  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
113581647  stag2; cohesin subunit SA-2 [KO:K06671]
113581676  [KO:K13376]
113582105  [KO:K06630]
113582122  cdca5; sororin [KO:K17390]
113582289  [KO:K06632] [EC:2.7.11.1]
113582354  e2f1; transcription factor E2F1 [KO:K17454]
113582454  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
113582494  pcna; proliferating cell nuclear antigen [KO:K04802]
113582509  cdc6; cell division control protein 6 homolog [KO:K02213]
113582603  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
113582707  [KO:K25163]
113582857  [KO:K21771]
113582875  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
113582960  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
113583195  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
113583358  e2f4; transcription factor E2F4 isoform X1 [KO:K04682]
113583571  [KO:K06624]
113583586  [KO:K06620]
113583707  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
113583718  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
113583945  [KO:K06619] [EC:2.7.10.2]
113584073  orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
113584255  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
113584344  [KO:K02542] [EC:5.6.2.3]
113584345  [KO:K03347]
113584643  [KO:K04728] [EC:2.7.11.1]
113584661  [KO:K04728] [EC:2.7.11.1]
113584974  ccnd2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
113585069  [KO:K23605]
113585246  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
113585421  [KO:K16197]
113585558  [KO:K11479] [EC:2.7.11.1]
113585931  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
113585995  [KO:K02541] [EC:5.6.2.3]
113586037  [KO:K04382] [EC:3.1.3.16]
113586489  [KO:K06626]
113586891  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
113586952  [KO:K10152]
113586971  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
113587067  e2f3; transcription factor E2F3 [KO:K06620]
113587099  mad2l1bp; MAD2L1-binding protein [KO:K26093]
113587140  [KO:K10152]
113587190  [KO:K06635]
113587267  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
113587655  [KO:K16198]
113587679  [KO:K21771]
113587712  [KO:K06067] [EC:3.5.1.98]
113587839  cdc27; cell division cycle protein 27 homolog [KO:K03350]
113587992  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
113588235  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
113588240  ccnb1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
113588400  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
113588422  [KO:K04503]
113588424  [KO:K03364]
113588458  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
113588625  fbxo5; F-box only protein 5 [KO:K10292]
113588714  [KO:K04682]
113588899  [KO:K02091] [EC:2.7.11.22]
113588909  orc6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
113588922  [KO:K04498] [EC:2.3.1.48]
113589241  [KO:K06636]
113589335  [KO:K04402]
113589390  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
113589690  orc2; origin recognition complex subunit 2 [KO:K02604]
113589820  [KO:K04377]
113589879  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
113590440  [KO:K04501]
113590455  cdc23; cell division cycle protein 23 homolog [KO:K03355]
113590474  cdc20; cell division cycle protein 20 homolog [KO:K03363]
113590492  [KO:K13375]
113590566  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
113590807  [KO:K04402]
113590822  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
113591025  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
113591255  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
113591321  cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
113591355  [KO:K03456]
113591781  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
113591806  [KO:K06672]
113591824  cdc16; cell division cycle protein 16 homolog [KO:K03353]
113591847  [KO:K04683]
113591978  [KO:K06671]
113592247  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
113592265  wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
113592272  [KO:K06671]
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
eee03030  DNA replication
eee04010  MAPK signaling pathway
eee04120  Ubiquitin mediated proteolysis
eee04210  Apoptosis
KO pathway
ko04110   

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