KEGG   PATHWAY: nfu04110
Entry
nfu04110                    Pathway                                
Name
Cell cycle - Nothobranchius furzeri (turquoise killifish)
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
nfu04110  Cell cycle
nfu04110

Other DBs
GO: 0000278
Organism
Nothobranchius furzeri (turquoise killifish) [GN:nfu]
Gene
107372320  [KO:K04402]
107372844  [KO:K22399]
107372925  cdca5; sororin [KO:K17390]
107373340  [KO:K06636]
107373442  [KO:K04382] [EC:3.1.3.16]
107373768  [KO:K22399]
107373814  [KO:K05866] [EC:3.1.3.48]
107373891  [KO:K04501]
107373962  nipbl; nipped-B-like protein [KO:K06672]
107374064  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
107374180  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
107374228  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
107374299  [KO:K06620]
107374449  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
107374962  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
107374991  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
107375004  skp2; S-phase kinase-associated protein 2 [KO:K03875]
107375027  [KO:K04402]
107375063  [KO:K04402]
107375104  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
107375282  cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
107375462  mad2l1bp; MAD2L1-binding protein [KO:K26093]
107375871  fbxo5; F-box only protein 5 [KO:K10292]
107375873  anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
107375931  wapl; wings apart-like protein homolog [KO:K25163]
107376237  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
107376330  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
107376331  ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
107376429  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
107376440  cdt1; DNA replication factor Cdt1 [KO:K10727]
107376486  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
107376716  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
107376866  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
107377000  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
107377009  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
107377116  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
107377392  tp53; cellular tumor antigen p53 [KO:K04451]
107377518  [KO:K13377]
107377547  [KO:K13376]
107377686  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
107377769  esco2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
107377797  casc5; protein CASC5 isoform X1 [KO:K11542]
107377863  [KO:K06635]
107378074  [KO:K11584]
107378199  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
107378559  [KO:K02091] [EC:2.7.11.22]
107378596  [KO:K10151]
107378720  mtbp; mdm2-binding protein [KO:K26116]
107378737  e2f3; transcription factor E2F3 isoform X1 [KO:K06620]
107378774  [KO:K06670]
107378872  [KO:K16197]
107378905  ttk; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
107379013  [KO:K04501]
107379284  ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
107379320  [KO:K11479] [EC:2.7.11.1]
107379349  stag3; cohesin subunit SA-3 [KO:K06671]
107379357  mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
107379731  dbf4; protein DBF4 homolog A [KO:K06629]
107379821  [KO:K13375]
107379996  [KO:K16198]
107380179  ccna2; cyclin-A2 [KO:K06627]
107380329  [KO:K03456]
107380467  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
107380541  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
107381480  [KO:K21770]
107382138  pds5a; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
107382298  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
107382426  cdc6; cell division control protein 6 homolog [KO:K02213]
107382539  myc; myc proto-oncogene protein [KO:K04377]
107382641  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
107383137  cul1; cullin-1 [KO:K03347]
107383310  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
107383619  [KO:K04682]
107383716  [KO:K04377]
107383877  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
107383974  cdc20; cell division cycle protein 20 homolog [KO:K03363]
107384036  espl1; separin [KO:K02365] [EC:3.4.22.49]
107384056  [KO:K06624]
107384088  [KO:K06625]
107384103  fzr1; fizzy-related protein homolog [KO:K03364]
107384278  orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
107384287  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
107384392  [KO:K03364]
107384684  orc4; origin recognition complex subunit 4 [KO:K02606]
107384733  [KO:K06671]
107384913  [KO:K16197]
107384967  rbl1; retinoblastoma-like protein 1 [KO:K04681]
107384993  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
107385060  [KO:K04377]
107385649  cdk4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
107385661  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
107385762  [KO:K06625]
107385769  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
107386136  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107386179  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
107386279  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
107386343  orc5; origin recognition complex subunit 5 [KO:K02607]
107386371  chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
107386428  cdc23; cell division cycle protein 23 homolog [KO:K03355]
107386518  rb1; retinoblastoma-associated protein [KO:K06618]
107386522  [KO:K06671]
107386557  [KO:K10779]
107386838  skp1; S-phase kinase-associated protein 1 [KO:K03094]
107386839  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107386911  ccna1; cyclin-A1 [KO:K06627]
107386918  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
107387033  [KO:K16198]
107387038  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
107387197  [KO:K06630]
107387371  [KO:K04402]
107387549  [KO:K02178] [EC:2.7.11.1]
107387799  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
107387826  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
107387863  [KO:K06629]
107387939  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
107388223  [KO:K04498] [EC:2.3.1.48]
107388329  [KO:K06636]
107388378  ticrr; treslin isoform X1 [KO:K26117]
107388400  [KO:K09993]
107388410  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
107388428  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
107388715  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
107388839  ddx11; probable ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
107389125  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
107389309  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
107389321  e2f4; transcription factor E2F4 [KO:K04682]
107389327  [KO:K10151]
107389352  wee2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
107389703  [KO:K06671]
107389708  cdc16; cell division cycle protein 16 homolog [KO:K03353]
107389808  tfdp1; transcription factor Dp-1 [KO:K04683]
107389867  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107389935  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
107389985  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
107390335  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
107390341  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
107390552  [KO:K04498] [EC:2.3.1.48]
107390725  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
107390864  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
107391080  [KO:K16197]
107391265  [KO:K06670]
107391318  e2f1; transcription factor E2F1 [KO:K17454]
107391644  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
107392030  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
107392063  stag1; cohesin subunit SA-1 [KO:K06671]
107392101  [KO:K04402]
107392211  e2f2; transcription factor E2F2 [KO:K09389]
107392234  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
107392252  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
107392287  ywhaq; 14-3-3 protein theta [KO:K16197]
107392404  tgfb3; transforming growth factor beta-3 [KO:K13377]
107392480  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
107392535  hdac1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
107393104  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
107393153  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
107393334  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
107393494  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
107393511  [KO:K04500]
107393593  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
107393877  ccnh; cyclin-H [KO:K06634]
107393916  cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
107394024  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
107394026  [KO:K06672]
107394046  [KO:K04501]
107394110  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
107394115  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
107394180  pcna; proliferating cell nuclear antigen [KO:K04802]
107394243  cdc45; cell division control protein 45 homolog [KO:K06628]
107394348  cdc20b; cell division cycle protein 20 homolog B [KO:K03363]
107394509  [KO:K06670]
107394684  [KO:K16197]
107394766  sgol1; shugoshin-like 1 [KO:K11580]
107395348  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
107395688  [KO:K02603]
107395689  cdc14a; dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
107395844  cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
107396099  anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
107396364  cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
107396382  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
107396561  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107397048  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
107397144  [KO:K06067] [EC:3.5.1.98]
107397237  [KO:K06630]
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
nfu03030  DNA replication
nfu04010  MAPK signaling pathway
nfu04120  Ubiquitin mediated proteolysis
nfu04210  Apoptosis
KO pathway
ko04110   

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