KEGG   PATHWAY: xla04110Help
Entry
xla04110                    Pathway                                

Name
Cell cycle - Xenopus laevis (African 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
BRITE hierarchy
Pathway map
Cell cycle
xla04110

All organismsOrtholog table
Module
Origin recognition complex [PATH:xla04110]
MCM complex [PATH:xla04110]
DNA-PK complex [PATH:xla04110]
DNA damage-induced cell cycle checkpoints [PATH:xla04110]
Cell cycle - G2/M transition [PATH:xla04110]
Other DBs
BSID: 
GO: 
Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
379161  
ccnd1-b; cyclin D1 [KO:K04503]
379937  
ccnd1-a; cyclin D1 [KO:K04503]
734882  
ccnd2-b; cyclin D2 [KO:K10151]
373667  
ccnd2-a; cyclin D2 [KO:K10151]
379406  
cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
496334  
cdk6; cyclin-dependent kinase 6 [KO:K02089] [EC:2.7.11.22]
431930  
rbl1; retinoblastoma-like 1 [KO:K04681]
379083  
hdac1-b; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
397868  
hdac1-a; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
399252  
hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
e2f1; E2F transcription factor 1 [KO:K17454]
398159  
e2f3; E2F transcription factor 3 [KO:K06620]
446541  
e2f4; E2F transcription factor 4, p107/p130-binding [KO:K04682]
494744  
tfdp1-a; transcription factor Dp-1 [KO:K04683]
447406  
tfdp1-b; transcription factor Dp-1 [KO:K04683]
tfdp2; transcription factor Dp-2 (E2F dimerization partner 2) [KO:K09392]
399097  
gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
397778  
tgfb1; transforming growth factor, beta 1 [KO:K13375]
373801  
tgfb2; transforming growth factor, beta 2 [KO:K13376]
432023  
smad2; SMAD family member 2 [KO:K04500]
399442  
mad2; Mad2 protein [KO:K04500]
378633  
smad3; SMAD family member 3 [KO:K04500]
403356  
smad4.2-a; SMAD family member 4, gene 2 [KO:K04501]
779167  
uncharacterized protein MGC79910; K04501 mothers against decapentaplegic homolog 4 [KO:K04501]
780764  
smad4.1; SMAD family member 4, gene 1 [KO:K04501]
379052  
myc-a; Transcriptional regulator Myc-A [KO:K04377]
399315  
myc; proto-oncogene c-myc II [KO:K04377]
735068  
zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
779240  
cdkn2b; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
446719  
cdkn2d; cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) [KO:K06623]
492306  
p16Xic3; cyclin dependent kinase inhibitor p16Xic3 [KO:K06624]
492305  
cdkn1a; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
380219  
ccne2; cyclin E2 [KO:K06626]
397840  
cycE1; cyclin E1 [KO:K06626]
495419  
uncharacterized LOC495419; K06626 cyclin E [KO:K06626]
397841  
ccne1; cyclin E1 [KO:K06626]
432036  
uncharacterized protein MGC81499; K02206 cyclin-dependent kinase 2 [EC:2.7.11.22] [KO:K02206] [EC:2.7.11.22]
399314  
cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
380538  
skp1; S-phase kinase-associated protein 1 [KO:K03094]
734414  
cul1; cullin 1 [KO:K03347]
734526  
uncharacterized protein MGC114992; K03347 cullin 1 [KO:K03347]
734901  
skp2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
397933  
Cyclin-A2; cyclin A2 [KO:K06627]
447494  
ccna1; cyclin A1 [KO:K06627]
734775  
ccna2; cyclin A2 [KO:K06627]
397885  
Cyclin-A1; cyclin A1 [KO:K06627]
398082  
xcdc6; Cdc6-related protein [KO:K02213]
403388  
cdc6; cell division cycle 6 [KO:K02213]
446991  
cdc45l; CDC45 cell division cycle 45-like (S. cerevisiae) [KO:K06628]
398081  
cdc45; cell division cycle 45 [KO:K06628]
398099  
cdc7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
398599  
dbf4; DBF4 zinc finger [KO:K06629]
380246  
cdk1-a; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
379785  
cdk1-b; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
398888  
uncharacterized protein MGC68601; K05868 cyclin B [KO:K05868]
397742  
ccnb1.2; cyclin B1 [KO:K05868]
379888  
ccnb1; cyclin B1 [KO:K05868]
379048  
ccnb3; cyclin B3 [KO:K05868]
398162  
cyclin B5; K05868 cyclin B [KO:K05868]
398163  
ccnb1; cyclin B1 [KO:K05868]
397743  
ccnb2; cyclin B2 [KO:K05868]
779404  
cycb3; cyclin B3 [KO:K05868]
cdc25b-a; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
cdc25b-b; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
398119  
cdc25c-b; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
397737  
cdc25c-a; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
cdc25c1; cell division cycle 25C1 [KO:K05867] [EC:3.1.3.48]
379809  
ywhaz-a; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta [KO:K16197]
380064  
ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta [KO:K16197]
399276  
ywhab-a; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta [KO:K16197]
379608  
ywhaz-b; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta [KO:K16197]
380457  
ywhab-b; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta [KO:K16197]
380397  
ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon [KO:K06630]
444832  
ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta [KO:K16198]
432005  
ywhag-b; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma [KO:K16198]
379724  
ywhag-a; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma [KO:K16198]
380481  
plk1; polo-like kinase 1 [KO:K06631] [EC:2.7.11.21]
399355  
wee1B; Wee1B kinase [KO:K06632] [EC:2.7.11.1]
398049  
wee1-a; wee1 homolog [KO:K06632] [EC:2.7.11.1]
398017  
wee2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
398396  
wee2a; wee1-like kinase [KO:K06632] [EC:2.7.11.1]
379626  
pkmyt1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
394356  
ccnh; cyclin H [KO:K06634]
399461  
cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.23 2.7.11.22]
443994  
cdc27; cell division cycle 27 [KO:K03350]
414530  
anapc4; anaphase promoting complex subunit 4 [KO:K03351]
779325  
anapc5; anaphase promoting complex subunit 5 [KO:K03352]
446982  
cdc16; cell division cycle 16 [KO:K03353]
446574  
anapc7; anaphase promoting complex subunit 7 [KO:K03354]
447726  
MGC81861 protein; K03354 anaphase-promoting complex subunit 7 [KO:K03354]
379580  
cdc23; cell division cycle 23 [KO:K03355]
380068  
cdc23; CDC23 (cell division cycle 23, yeast, homolog) [KO:K03355]
595046  
uncharacterized LOC595046; K03357 anaphase-promoting complex subunit 10 [KO:K03357]
734319  
anapc10; anaphase promoting complex subunit 10 [KO:K03357]
496247  
anapc11; anaphase promoting complex subunit 11 [KO:K03358]
anapc13.2; anaphase promoting complex subunit 13, gene 2 [KO:K12456]
379130  
cdc20; cell division cycle 20 homolog [KO:K03363]
398044  
cdc20; cell division cycle 20 [KO:K03363]
398156  
securin; K06635 securin [KO:K06635]
380182  
smc1a; structural maintenance of chromosomes 1A [KO:K06636]
399092  
smc3; structural maintenance of chromosomes 3 [KO:K06669]
399163  
stag3l4; stromal antigen 3-like 4 [KO:K06671]
495133  
stag1; stromal antigen 1 [KO:K06671]
394319  
stag2; stromal antigen 2 [KO:K06671]
734633  
uncharacterized protein MGC114996; K06671 cohesin complex subunit SA-1/2 [KO:K06671]
399129  
rad21; 14S cohesin RAD21 subunit [KO:K06670]
503676  
rad21; RAD21 homolog (S. pombe) [KO:K06670]
398219  
ttk; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
398234  
bub1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
399106  
bub3; BUB3 mitotic checkpoint protein [KO:K02180]
378923  
bub1b; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
394307  
mad1-A; spindle checkpoint protein Xmad1 [KO:K06638]
414724  
uncharacterized protein MGC81153; K02537 mitotic spindle assembly checkpoint protein MAD2 [KO:K02537]
380433  
mad2l1; MAD2 mitotic arrest deficient-like 1 [KO:K02537]
394380  
mad2l2; MAD2 mitotic arrest deficient-like 2 [KO:K13728]
380351  
fzr1; fizzy/cell division cycle 20 related 1 [KO:K03364]
403393  
cdc14a; cell division cycle 14A [KO:K06639] [EC:3.1.3.48 3.1.3.16]
407839  
cdc14b; cell division cycle 14B [KO:K06639] [EC:3.1.3.48 3.1.3.16]
398197  
atr; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
398148  
atm; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
397926  
tp53; tumor protein p53 [KO:K04451]
398191  
chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
398179  
chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
495689  
crebbp-b; CREB binding protein [KO:K04498] [EC:2.3.1.48]
373602  
prkdc; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
444499  
mdm2; MDM2 proto-oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
379224  
gadd45a; growth arrest and DNA-damage-inducible, alpha [KO:K04402]
399196  
gadd45g; growth arrest and DNA-damage-inducible, gamma [KO:K04402]
379285  
uncharacterized protein MGC53682; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
Gadd45beta; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
398425  
MGC53867; Proliferating cell nuclear antigen-like [KO:K04802]
394328  
pcna; proliferating cell nuclear antigen [KO:K04802]
398141  
tyrosine phosphatase Cdc25A; K06645 M-phase inducer phosphatase 1 [EC:3.1.3.48] [KO:K06645] [EC:3.1.3.48]
734734  
cdc25a; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
398063  
orc1; origin recognition complex, subunit 1 [KO:K02603]
394365  
orc2; origin recognition complex, subunit 2 [KO:K02604]
379084  
orc3; origin recognition complex, subunit 3 [KO:K02605]
397923  
orc4; origin recognition complex, subunit 4 [KO:K02606]
734494  
orc5; origin recognition complex, subunit 5 [KO:K02607]
446747  
orc6; origin recognition complex, subunit 6 [KO:K02608]
380451  
mcm2; minichromosome maintenance complex component 2 [KO:K02540] [EC:3.6.4.12]
379850  
mcm3; MCM3 minichromosome maintenance deficient 3 (S. cerevisiae) [KO:K02541] [EC:3.6.4.12]
397821  
mcm3; minichromosome maintenance complex component 3 [KO:K02541] [EC:3.6.4.12]
397843  
mcm4-b; minichromosome maintenance complex component 4 [KO:K02212] [EC:3.6.4.12]
373601  
mcm4-a; minichromosome maintenance complex component 4 [KO:K02212] [EC:3.6.4.12]
380587  
mcm5-a; minichromosome maintenance complex component 5 [KO:K02209] [EC:3.6.4.12]
379699  
mcm5-b; minichromosome maintenance complex component 5 [KO:K02209] [EC:3.6.4.12]
380282  
mcm6.2-b; minichromosome maintenance complex component 6 [KO:K02542] [EC:3.6.4.12]
398071  
mcm6; minichromosome maintenance complex component 6 [KO:K02542] [EC:3.6.4.12]
397852  
mcm7-a; minichromosome maintenance complex component 7 [KO:K02210] [EC:3.6.4.12]
380414  
mcm7-b; minichromosome maintenance complex component 7 [KO:K02210] [EC:3.6.4.12]
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)
Reference
  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)
Reference
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
Oncogene 24:2796-809 (2005)
Reference
  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)
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)
Reference
  Authors
Klein EA, Assoian RK
  Title
Transcriptional regulation of the cyclin D1 gene at a glance.
  Journal
J Cell Sci 121:3853-7 (2008)
Reference
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
  Journal
Genes Dev 13:1501-12 (1999)
Reference
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
Reference
  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)
Reference
  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)
Reference
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
Reference
  Authors
Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
  Journal
Nature 408:307-10 (2000)
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)
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)
Reference
  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)
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)
Reference
  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)
Reference
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
  Journal
Nat Rev Mol Cell Biol 8:379-93 (2007)
Reference
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
Reference
  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)
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)
KO pathway
 

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