KEGG   PATHWAY: xtr04110
Entry
xtr04110                    Pathway                                
Name
Cell cycle - Xenopus tropicalis (tropical clawed frog)
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
xtr04110  Cell cycle
xtr04110

Other DBs
GO: 0000278
Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
100036608  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
100038054  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
100038071  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
100038079  e2f4; transcription factor E2F4 [KO:K04682]
100038088  smad4.1; mothers against decapentaplegic homolog 4 [KO:K04501]
100038224  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100038237  nipbl; nipped-B-like protein isoform X1 [KO:K06672]
100101677  crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100101736  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100101792  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100124300  cdc25c; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
100125106  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
100125126  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100125170  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
100125181  orc3; origin recognition complex subunit 3 [KO:K02605]
100126066  tfdp2; transcription factor Dp-2 [KO:K09392]
100135123  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
100135353  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
100135357  sgo1; shugoshin 1 [KO:K11580]
100144705  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
100144952  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
100144958  fzr1; fizzy-related protein homolog [KO:K03364]
100145078  cdca5; sororin [KO:K17390]
100145425  smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
100145524  wee1; uncharacterized protein LOC100145524 [KO:K06632] [EC:2.7.11.1]
100145561  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
100145671  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
100145798  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
100151699  e2f5; transcription factor E2F5 [KO:K04682]
100158523  stag1; cohesin subunit SA-1 [KO:K06671]
100158558  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
100158601  mcm3; maternal DNA replication licensing factor mcm3 isoform X2 [KO:K02541] [EC:5.6.2.3]
100158636  espl1; separin [KO:K02365] [EC:3.4.22.49]
100170169  wapl; wings apart-like protein homolog [KO:K25163]
100188925  smad4.2; mothers against decapentaplegic homolog 4 [KO:K04501]
100216140  rbl1; retinoblastoma-like protein 1 [KO:K04681]
100216159  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
100216169  skp2; S-phase kinase-associated protein 2 [KO:K03875]
100270772  ccnb2; cyclin B2 [KO:K21770]
100379784  stag2; cohesin subunit SA-2 [KO:K06671]
100379812  cdt1; DNA replication factor Cdt1 [KO:K10727]
100379935  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100379975  dbf4b; protein DBF4 homolog B isoform X4 [KO:K06629]
100380046  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
100486631  [KO:K06671]
100486914  mad2l1bp; MAD2L1-binding protein [KO:K26093]
100487013  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100488663  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
100489448  ticrr; treslin [KO:K26117]
100489648  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100489680  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
100489734  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100490252  cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100490373  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100490474  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
100490767  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100490771  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100492023  rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
100493114  rb1; retinoblastoma-associated protein [KO:K06618]
100493711  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
100493924  e2f1; transcription factor E2F1 [KO:K17454]
100494390  anapc13.2; anaphase-promoting complex subunit 13 [KO:K12456]
100494711  ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
100495593  atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
100497601  knl1; protein CASC5 [KO:K11542]
100498430  tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
100498440  [KO:K06635]
101731339  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
101732126  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116408221  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
394448  [KO:K21770]
394503  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
394542  cdc20; cell division cycle protein 20 homolog [KO:K03363]
394726  ccnb1.2; cyclin B1 [KO:K05868]
394780  ywhaz; 14-3-3 protein zeta [KO:K16197]
394836  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
394853  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform 1 [KO:K06643] [EC:2.3.2.27]
394858  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
394864  ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
394888  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
395024  myc; myc proto-oncogene protein [KO:K04377]
395030  mcm6.2; zygotic DNA replication licensing factor mcm6 [KO:K02542] [EC:5.6.2.3]
395042  ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
407937  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
407945  mcm7; DNA replication licensing factor mcm7 [KO:K02210] [EC:5.6.2.3]
431679  tp53; cellular tumor antigen p53 [KO:K04451]
447953  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
447995  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
448031  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
448045  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
448122  mad2l2; mitotic spindle assembly checkpoint protein MAD2B isoform 1 [KO:K13728]
448135  orc4; origin recognition complex subunit 4 [KO:K02606]
448137  mcm4; DNA replication licensing factor mcm4 [KO:K02212] [EC:5.6.2.3]
448194  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
448442  gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
448454  ccna2; cyclin-A2 [KO:K06627]
448458  mcm2; DNA replication licensing factor mcm2 [KO:K02540] [EC:5.6.2.3]
448463  ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
448547  cdc16; cell division cycle protein 16 homolog [KO:K03353]
448767  cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
448774  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
493192  ddx11; probable ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
493224  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
493272  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
493302  pcna; proliferating cell nuclear antigen [KO:K04802]
493326  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
493356  cdc6; cell division control protein 6 homolog [KO:K02213]
493498  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
493518  ywhae; 14-3-3 protein epsilon [KO:K06630]
496522  e2f3; transcription factor E2F3 [KO:K06620]
496529  ywhab; 14-3-3 protein beta/alpha [KO:K16197]
496558  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
496580  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
496586  smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
496610  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
548681  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
548862  ccndx; cyclin Dx [KO:K04503]
548888  tfdp1; transcription factor Dp-1 [KO:K04683]
548905  gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
548975  mcm6; maternal DNA replication licensing factor mcm6 [KO:K02542] [EC:5.6.2.3]
548993  ccna1; cyclin-A1 [KO:K06627]
549010  ccnh; cyclin-H [KO:K06634]
549021  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
549081  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
549082  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
549146  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
549273  skp1; S-phase kinase-associated protein 1 [KO:K03094]
549335  cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
549496  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
549513  cdc23; cell division cycle protein 23 homolog [KO:K03355]
549613  aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
549622  ywhah; 14-3-3 protein eta [KO:K16198]
549767  orc5; origin recognition complex subunit 5 [KO:K02607]
549939  orc6; origin recognition complex subunit 6 [KO:K02608]
549973  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
549994  anapc13.1; anaphase-promoting complex subunit 13 [KO:K12456]
550081  mcm5; DNA replication licensing factor mcm5 [KO:K02209] [EC:5.6.2.3]
594953  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
594958  ywhaq; 14-3-3 protein theta [KO:K16197]
733526  esco1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
733555  fbxo5; F-box only protein 5 [KO:K10292]
733733  cdc14b; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
733748  dbf4; protein DBF4 homolog A [KO:K06629]
733851  cdc25a; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
734023  ep300; histone acetyltransferase p300 isoform X4 [KO:K04498] [EC:2.3.1.48]
734048  orc1; origin recognition complex subunit 1 [KO:K02603]
734092  mcm3; zygotic DNA replication licensing factor mcm3 [KO:K02541] [EC:5.6.2.3]
734121  cul1; cullin-1 [KO:K03347]
779505  mtbp; mdm2-binding protein [KO:K26116]
779545  cdc45; cell division control protein 45 homolog [KO:K06628]
779762  ywhag; 14-3-3 protein gamma [KO:K16198]
779925  cdc27; cell division cycle protein 27 homolog [KO:K03350]
780054  ttk; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
780267  orc2; origin recognition complex subunit 2 [KO:K02604]
780291  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
780300  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
780327  anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
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
xtr03030  DNA replication
xtr04010  MAPK signaling pathway
xtr04120  Ubiquitin mediated proteolysis
xtr04210  Apoptosis
KO pathway
ko04110   

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