KEGG   PATHWAY: mdo04110Help
mdo04110                    Pathway                                

Cell cycle - Monodelphis domestica (opossum)
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.
Cellular Processes; Cell growth and death
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Cell cycle

All organismsOrtholog table
Origin recognition complex [PATH:mdo04110]
MCM complex [PATH:mdo04110]
SCF-SKP2 complex [PATH:mdo04110]
APC/C complex [PATH:mdo04110]
Other DBs
Monodelphis domestica (opossum) [GN:mdo]
g1/S-specific cyclin-D1-like; K04503 cyclin D1 [KO:K04503]
g1/S-specific cyclin-D2-like; K10151 cyclin D2 [KO:K10151]
g1/S-specific cyclin-D3-like; K10152 cyclin D3 [KO:K10152]
cyclin-dependent kinase 6-like; K02091 cyclin-dependent kinase 6 [EC:] [KO:K02091] [EC:]
RB1; retinoblastoma 1 [KO:K06618]
retinoblastoma-like protein 1-like; K04681 retinoblastoma-like protein 1 [KO:K04681]
RBL2; retinoblastoma-like 2 (p130) [KO:K16332]
ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:]
histone deacetylase 2-like; K06067 histone deacetylase 1/2 [EC:] [KO:K06067] [EC:]
transcription factor E2F1-like; K17454 transcription factor E2F1 [KO:K17454]
transcription factor E2F2-like; K09389 transcription factor E2F2 [KO:K09389]
E2F3; E2F transcription factor 3 [KO:K06620]
transcription factor E2F4-like; K04682 transcription factor E2F4/5 [KO:K04682]
transcription factor E2F5-like; K04682 transcription factor E2F4/5 [KO:K04682]
TFDP1; transcription factor Dp-1 [KO:K04683]
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
transforming growth factor beta-1-like; K13375 transforming growth factor beta-1 [KO:K13375]
transforming growth factor beta-2-like; K13376 transforming growth factor beta-2 [KO:K13376]
TGFB3; transforming growth factor, beta 3 [KO:K13377]
SMAD2; SMAD family member 2 [KO:K04500]
SMAD3; SMAD family member 3 [KO:K04500]
mothers against decapentaplegic homolog 4-like; K04501 mothers against decapentaplegic homolog 4 [KO:K04501]
myc proto-oncogene protein-like; K04377 Myc proto-oncogene protein [KO:K04377]
zinc finger and BTB domain-containing protein 17-like; K10500 zinc finger and BTB domain-containing protein 17 [KO:K10500]
cyclin-dependent kinase 4 inhibitor B-like; K04685 cyclin-dependent kinase inhibitor 2B [KO:K04685]
cyclin-dependent kinase 4 inhibitor C-like; K06622 cyclin-dependent kinase inhibitor 2C [KO:K06622]
cyclin-dependent kinase 4 inhibitor D-like; K06623 cyclin-dependent kinase inhibitor 2D [KO:K06623]
CDKN1B; cyclin-dependent kinase inhibitor 1B (p27, Kip1) [KO:K06624]
cyclin-dependent kinase inhibitor 1-like; K06625 cyclin-dependent kinase inhibitor 1A [KO:K06625]
uncharacterized LOC100014623; K06626 cyclin E [KO:K06626]
g1/S-specific cyclin-E2-like; K06626 cyclin E [KO:K06626]
s-phase kinase-associated protein 1-like; K03094 S-phase kinase-associated protein 1 [KO:K03094]
cullin-1-like; K03347 cullin 1 [KO:K03347]
e3 ubiquitin-protein ligase RBX1-like; K03868 RING-box protein 1 [KO:K03868]
s-phase kinase-associated protein 2-like; K03875 F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2) [KO:K03875]
CCNA1; cyclin A1 [KO:K06627]
cyclin-A2-like; K06627 cyclin A [KO:K06627]
CDC6; cell division cycle 6 homolog (S. cerevisiae) [KO:K02213]
CDC45; cell division cycle 45 homolog (S. cerevisiae) [KO:K06628]
CDC7; cell division cycle 7 homolog (S. cerevisiae) [KO:K02214] [EC:]
DBF4; DBF4 homolog (S. cerevisiae) [KO:K06629]
cyclin-dependent kinase 1-like; K02087 cyclin-dependent kinase 1 [EC:] [KO:K02087] [EC:]
g2/mitotic-specific cyclin-B1-like; K05868 cyclin B [KO:K05868]
g2/mitotic-specific cyclin-B2-like; K05868 cyclin B [KO:K05868]
14-3-3 protein zeta/delta-like; K16197 14-3-3 protein beta/theta/zeta [KO:K16197]
14-3-3 protein beta/alpha-like; K16197 14-3-3 protein beta/theta/zeta [KO:K16197]
14-3-3 protein theta-like; K16197 14-3-3 protein beta/theta/zeta [KO:K16197]
14-3-3 protein eta-like; K16198 14-3-3 protein gamma/eta [KO:K16198]
14-3-3 protein gamma-like; K16198 14-3-3 protein gamma/eta [KO:K16198]
serine/threonine-protein kinase PLK1-like; K06631 polo-like kinase 1 [EC:] [KO:K06631] [EC:]
WEE1; WEE1 homolog (S. pombe) [KO:K06632] [EC:]
wee1-like protein kinase 2-like; K06632 wee1-like protein kinase [EC:] [KO:K06632] [EC:]
membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase-like; K06633 membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [EC:] [KO:K06633] [EC:]
cyclin-H-like; K06634 cyclin H [KO:K06634]
CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:]
ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
CDC27; cell division cycle 27 homolog (S. cerevisiae) [KO:K03350]
ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
CDC16; cell division cycle 16 homolog (S. cerevisiae) [KO:K03353]
ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
CDC23; cell division cycle 23 homolog (S. cerevisiae) [KO:K03355]
anaphase-promoting complex subunit 10-like; K03357 anaphase-promoting complex subunit 10 [KO:K03357]
anaphase-promoting complex subunit 11-like; K03358 anaphase-promoting complex subunit 11 [KO:K03358]
anaphase-promoting complex subunit 13-like; K12456 anaphase-promoting complex subunit 13 [KO:K12456]
cell division cycle protein 20 homolog; K03363 cell division cycle 20, cofactor of APC complex [KO:K03363]
securin-like; K06635 securin [KO:K06635]
ESPL1; extra spindle pole bodies homolog 1 (S. cerevisiae) [KO:K02365] [EC:]
SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
structural maintenance of chromosomes protein 1A-like; K06636 structural maintenance of chromosome 1 [KO:K06636]
SMC3; structural maintenance of chromosomes 3 [KO:K06669]
STAG2; stromal antigen 2 [KO:K06671]
STAG1; stromal antigen 1 [KO:K06671]
cohesin subunit SA-2-like; K06671 cohesin complex subunit SA-1/2 [KO:K06671]
RAD21; RAD21 homolog (S. pombe) [KO:K06670]
TTK; TTK protein kinase [KO:K08866] [EC:]
BUB1; budding uninhibited by benzimidazoles 1 homolog (yeast) [KO:K02178] [EC:]
BUB3; budding uninhibited by benzimidazoles 3 homolog (yeast) [KO:K02180]
BUB1B; budding uninhibited by benzimidazoles 1 homolog beta (yeast) [KO:K06637] [EC:]
MAD1L1; MAD1 mitotic arrest deficient-like 1 (yeast) [KO:K06638]
mitotic spindle assembly checkpoint protein MAD1-like; K06638 mitotic spindle assembly checkpoint protein MAD1 [KO:K06638]
mitotic spindle assembly checkpoint protein MAD2A-like; K02537 mitotic spindle assembly checkpoint protein MAD2 [KO:K02537]
mitotic spindle assembly checkpoint protein MAD2B-like; K13728 mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
fizzy-related protein homolog; K03364 cell division cycle 20-like protein 1, cofactor of APC complex [KO:K03364]
fizzy-related protein homolog; K03364 cell division cycle 20-like protein 1, cofactor of APC complex [KO:K03364]
dual specificity protein phosphatase CDC14B-like; K06639 cell division cycle 14 [EC:] [KO:K06639] [EC:]
CDC14A; CDC14 cell division cycle 14 homolog A (S. cerevisiae) [KO:K06639] [EC:]
ATR; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:]
ATM; ataxia telangiectasia mutated [KO:K04728] [EC:]
TP53; tumor protein p53 [KO:K04451]
CHEK1; checkpoint kinase 1 [KO:K02216] [EC:]
serine/threonine-protein kinase Chk2-like; K06641 serine/threonine-protein kinase Chk2 [EC:] [KO:K06641] [EC:]
EP300; E1A binding protein p300 [KO:K04498] [EC:]
CREBBP; CREB binding protein [KO:K04498] [EC:]
e3 ubiquitin-protein ligase Mdm2-like; K06643 E3 ubiquitin-protein ligase Mdm2 [EC:] [KO:K06643] [EC:]
growth arrest and DNA damage-inducible protein GADD45 gamma-like; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
growth arrest and DNA damage-inducible protein GADD45 alpha-like; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
growth arrest and DNA damage-inducible protein GADD45 beta-like; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
proliferating cell nuclear antigen-like; K04802 proliferating cell nuclear antigen [KO:K04802]
14-3-3 protein sigma-like; K06644 stratifin [KO:K06644]
CDC25A; cell division cycle 25 homolog A (S. pombe) [KO:K06645] [EC:]
origin recognition complex subunit 1-like; K02603 origin recognition complex subunit 1 [KO:K02603]
ORC2; origin recognition complex, subunit 2 [KO:K02604]
origin recognition complex subunit 3-like; K02605 origin recognition complex subunit 3 [KO:K02605]
origin recognition complex subunit 4-like; K02606 origin recognition complex subunit 4 [KO:K02606]
ORC5; origin recognition complex, subunit 5 [KO:K02607]
origin recognition complex subunit 6-like; K02608 origin recognition complex subunit 6 [KO:K02608]
MCM7; minichromosome maintenance complex component 7 [KO:K02540] [EC:]
DNA replication licensing factor MCM3-like; K02541 DNA replication licensing factor MCM3 [EC:] [KO:K02541] [EC:]
MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:]
MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:]
DNA replication licensing factor MCM6-like; K02542 DNA replication licensing factor MCM6 [EC:] [KO:K02542] [EC:]
MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:]
Matsuoka S, Yamaguchi M, Matsukage A
D-type cyclin-binding regions of proliferating cell nuclear antigen.
J Biol Chem 269:11030-6 (1994)
Welch PJ, Wang JY
A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
Cell 75:779-90 (1993)
Macaluso M, Montanari M, Giordano A
Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes.
Oncogene 25:5263-7 (2006)
Cobrinik D
Pocket proteins and cell cycle control.
Oncogene 24:2796-809 (2005)
Boutros R, Lobjois V, Ducommun B
CDC25 phosphatases in cancer cells: key players? Good targets?
Nat Rev Cancer 7:495-507 (2007)
Diehl JA, Cheng M, Roussel MF, Sherr CJ
Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.
Genes Dev 12:3499-511 (1998)
Klein EA, Assoian RK
Transcriptional regulation of the cyclin D1 gene at a glance.
J Cell Sci 121:3853-7 (2008)
Sherr CJ, Roberts JM
CDK inhibitors: positive and negative regulators of G1-phase progression.
Genes Dev 13:1501-12 (1999)
Shi Y, Massague J.
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
Cell 113:685-700 (2003)
Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, Hatakeyama S, Nakayama K, Nakayama KI
Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation.
Proc Natl Acad Sci U S A 100:10231-6 (2003)
Bond M, Sala-Newby GB, Wu YJ, Newby AC
Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
Cardiovasc Res 69:198-206 (2006)
Harris SL, Levine AJ.
The p53 pathway: positive and negative feedback loops.
Oncogene 24:2899-908 (2005)
Vogelstein B, Lane D, Levine AJ
Surfing the p53 network.
Nature 408:307-10 (2000)
Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
Science 266:1376-80 (1994)
Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
EMBO J 18:396-410 (1999)
Sheu YJ, Stillman B
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
Mol Cell 24:101-13 (2006)
Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M
Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity.
EMBO J 16:343-54 (1997)
Lolli G, Johnson LN
CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?
Cell Cycle 4:572-7 (2005)
Musacchio A, Salmon ED
The spindle-assembly checkpoint in space and time.
Nat Rev Mol Cell Biol 8:379-93 (2007)
Uhlmann F
Chromosome cohesion and separation: from men and molecules.
Curr Biol 13:R104-14 (2003)
Stegmeier F, Amon A
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
Annu Rev Genet 38:203-32 (2004)
Moustakas A, Kardassis D
Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
Proc Natl Acad Sci U S A 95:6733-8 (1998)
KO pathway

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