KEGG   PATHWAY: pret04110
Entry
pret04110                   Pathway                                
Name
Cell cycle - Poecilia reticulata (guppy)
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
pret04110  Cell cycle
pret04110

Other DBs
GO: 0000278
Organism
Poecilia reticulata (guppy) [GN:pret]
Gene
103456842  myc; myc proto-oncogene protein isoform X1 [KO:K04377]
103457010  cul1; cullin-1 [KO:K03347]
103457093  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
103457167  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
103457270  esco2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
103457322  knl1; protein CASC5 [KO:K11542]
103457415  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
103457452  orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
103457593  [KO:K13377]
103457772  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
103457918  [KO:K11584]
103458004  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103458087  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103458266  cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
103458425  stag1; cohesin subunit SA-1 [KO:K06671]
103458428  atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
103458442  [KO:K04402]
103458557  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
103458631  [KO:K06067] [EC:3.5.1.98]
103458812  orc3; origin recognition complex subunit 3 [KO:K02605]
103458830  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X3 [KO:K11584]
103458855  e2f2; transcription factor E2F2 isoform X1 [KO:K09389]
103458870  ywhaq; 14-3-3 protein theta [KO:K16197]
103459051  tgfb3; transforming growth factor beta-3 [KO:K13377]
103459095  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103459107  orc5; origin recognition complex subunit 5 [KO:K02607]
103459164  [KO:K10151]
103459498  [KO:K06625]
103459499  [KO:K06624]
103459583  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103459979  skp1; S-phase kinase-associated protein 1 [KO:K03094]
103459981  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103460374  rbl1; retinoblastoma-like protein 1 [KO:K04681]
103460387  chek2; serine/threonine-protein kinase Chk2 isoform X2 [KO:K06641] [EC:2.7.11.1]
103460432  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
103460619  [KO:K04377]
103460661  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
103460818  [KO:K21770]
103461259  [KO:K13728]
103462043  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
103462102  [KO:K23605]
103462253  ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
103462287  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
103462556  [KO:K04682]
103462656  rbl2; retinoblastoma-like protein 2 [KO:K04681]
103462748  [KO:K09993]
103463150  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103463163  cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103463240  orc1; origin recognition complex subunit 1 [KO:K02603]
103463438  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
103463695  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
103463857  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
103463991  [KO:K04402]
103464068  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
103464091  [KO:K04498] [EC:2.3.1.48]
103464190  [KO:K06622]
103464233  [KO:K04377]
103464293  [KO:K16197]
103464315  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
103465178  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
103465183  [KO:K06625]
103465316  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
103465328  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103465369  espl1; separin [KO:K02365] [EC:3.4.22.49]
103465692  ticrr; treslin isoform X1 [KO:K26117]
103465727  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
103465732  [KO:K06636]
103465804  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
103465909  [KO:K06624]
103465931  [KO:K09993]
103466455  cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103466539  [KO:K23605]
103466671  ddx11; probable ATP-dependent DNA helicase DDX11 isoform X2 [KO:K11273] [EC:3.6.4.13]
103466787  [KO:K16332]
103466812  [KO:K10151]
103466817  e2f4; transcription factor E2F4 [KO:K04682]
103466827  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
103466851  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
103466857  e2f1; transcription factor E2F1 [KO:K17454]
103467021  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
103467081  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
103467334  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
103467546  [KO:K16197]
103467726  [KO:K06670]
103468297  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
103468459  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
103468460  [KO:K04498] [EC:2.3.1.48]
103468517  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
103469031  cdc27; cell division cycle protein 27 homolog isoform X2 [KO:K03350]
103469079  [KO:K10151]
103469191  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
103469340  [KO:K02091] [EC:2.7.11.22]
103469523  anapc7; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 7 [KO:K03354]
103469686  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
103469777  [KO:K04500]
103470044  cdc45; cell division control protein 45 homolog [KO:K06628]
103470056  pcna; proliferating cell nuclear antigen [KO:K04802]
103470128  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103470135  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103470200  [KO:K04501]
103470223  nipbl; nipped-B-like protein isoform X4 [KO:K06672]
103470224  ndc80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
103470364  cdc6; cell division control protein 6 homolog [KO:K02213]
103470403  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
103470444  ccnh; cyclin-H [KO:K06634]
103470779  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X2 [KO:K04382] [EC:3.1.3.16]
103470908  [KO:K06671]
103471193  [KO:K04382] [EC:3.1.3.16]
103471215  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
103471446  tgfb2; transforming growth factor beta-2 [KO:K13376]
103471492  stag3; cohesin subunit SA-3 isoform X1 [KO:K06671]
103471493  mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
103471497  [KO:K11479] [EC:2.7.11.1]
103471545  pttg1; securin [KO:K06635]
103471861  ccna2; cyclin-A2 [KO:K06627]
103472045  [KO:K06067] [EC:3.5.1.98]
103472053  [KO:K06620]
103472249  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103472354  sgo1; shugoshin-like 1 [KO:K11580]
103472446  [KO:K16197]
103472890  [KO:K06670]
103473081  cdca5; sororin [KO:K17390]
103473773  [KO:K04501]
103473783  [KO:K06672]
103473791  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
103473942  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103474023  [KO:K04402]
103474062  skp2; S-phase kinase-associated protein 2 [KO:K03875]
103474138  [KO:K16198]
103474390  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
103474472  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
103474595  ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
103474790  [KO:K21770]
103474877  ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
103475119  [KO:K13375]
103475471  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
103475564  ccna1; cyclin-A1 [KO:K06627]
103475573  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
103475723  [KO:K10779]
103475746  [KO:K06671]
103475763  [KO:K06618]
103475850  cdc23; cell division cycle protein 23 homolog [KO:K03355]
103475858  [KO:K06618]
103476068  [KO:K16198]
103476437  fbxo5; F-box only protein 5 [KO:K10292]
103476439  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
103476652  cdk1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103476663  cdt1; DNA replication factor Cdt1 [KO:K10727]
103476704  [KO:K25163]
103477225  mad2l1bp; MAD2L1-binding protein [KO:K26093]
103477404  ppp2r5d; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103477474  [KO:K04501]
103477592  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
103478132  dbf4; protein DBF4 homolog A [KO:K06629]
103478248  ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
103478347  [KO:K06670]
103478383  e2f3; transcription factor E2F3 isoform X1 [KO:K06620]
103478400  mtbp; mdm2-binding protein isoform X3 [KO:K26116]
103478601  trip13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
103478834  [KO:K16197]
103478844  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
103478852  orc2; origin recognition complex subunit 2 [KO:K02604]
103478963  [KO:K06671]
103479019  [KO:K03364]
103479028  cdc16; cell division cycle protein 16 homolog [KO:K03353]
103479116  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
103479130  gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
103479248  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103479443  [KO:K03364]
103479604  cdc20; cell division cycle protein 20 homolog [KO:K03363]
103479683  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
103479806  [KO:K04682]
103480064  tfdp1; transcription factor Dp-1 [KO:K04683]
103480085  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
103480404  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
103480413  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
103480460  tp53; cellular tumor antigen p53 [KO:K04451]
103480751  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
103480831  anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
103481185  wee2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
103481268  [KO:K06629]
103481455  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
103481579  bub3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
103481872  [KO:K25163]
103482005  [KO:K04498] [EC:2.3.1.48]
103482327  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
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
pret03030  DNA replication
pret04010  MAPK signaling pathway
pret04120  Ubiquitin mediated proteolysis
pret04210  Apoptosis
KO pathway
ko04110   

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