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]
DNA-PK complex [PATH:mdo04110]
SCF-SKP2 complex [PATH:mdo04110]
APC/C complex [PATH:mdo04110]
DNA damage-induced cell cycle checkpoints [PATH:mdo04110]
Cell cycle - G2/M transition [PATH:mdo04110]
Other DBs
Monodelphis domestica (opossum) [GN:mdo]
CCND1; cyclin D1 [KO:K04503]
CCND2; cyclin D2 [KO:K10151]
CCND3; cyclin D3 [KO:K10152]
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:]
RB1; retinoblastoma 1 [KO:K06618]
RBL1; retinoblastoma-like 1 [KO:K04681]
RBL2; retinoblastoma-like 2 [KO:K16332]
ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:]
HDAC2; histone deacetylase 2 [KO:K06067] [EC:]
HDAC1; histone deacetylase 1 [KO:K06067] [EC:]
E2F1; E2F transcription factor 1 [KO:K17454]
E2F2; E2F transcription factor 2 [KO:K09389]
E2F3; E2F transcription factor 3 [KO:K06620]
E2F4; E2F transcription factor 4, p107/p130-binding [KO:K04682]
E2F5; E2F transcription factor 5, p130-binding [KO:K04682]
TFDP1; transcription factor Dp-1 [KO:K04683]
TFDP2; transcription factor Dp-2 (E2F dimerization partner 2) [KO:K09392]
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
TGFB1; transforming growth factor, beta 1 [KO:K13375]
TGFB2; 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]
SMAD4; SMAD family member 4 [KO:K04501]
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
CDKN2B; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
CDKN2C; cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) [KO:K06622]
CDKN2D; cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) [KO:K06623]
CDKN1B; cyclin-dependent kinase inhibitor 1B (p27, Kip1) [KO:K06624]
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
CCNE1; cyclin E1 [KO:K06626]
CCNE2; cyclin E2 [KO:K06626]
SKP1; S-phase kinase-associated protein 1 [KO:K03094]
CUL1; cullin 1 [KO:K03347]
RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
SKP2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
CCNA1; cyclin A1 [KO:K06627]
CCNA2; cyclin A2 [KO:K06627]
CDC6; cell division cycle 6 [KO:K02213]
CDC45; cell division cycle 45 [KO:K06628]
CDC7; cell division cycle 7 [KO:K02214] [EC:]
DBF4; DBF4 zinc finger [KO:K06629]
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:]
CCNB1; cyclin B1 [KO:K05868]
CCNB2; cyclin B2 [KO:K05868]
CCNB3; cyclin B3 [KO:K05868]
CDC25C; cell division cycle 25C [KO:K05867] [EC:]
YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta [KO:K16197]
YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta [KO:K16197]
YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta [KO:K16197]
YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon [KO:K06630]
YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta [KO:K16198]
YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma [KO:K16198]
PLK1; polo-like kinase 1 [KO:K06631] [EC:]
WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:]
WEE2; WEE1 homolog 2 (S. pombe) [KO:K06632] [EC:]
PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:]
CCNH; 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 protein 27 homolog-like [KO:K03350]
ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
CDC16; cell division cycle 16 [KO:K03353]
ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
CDC23; cell division cycle 23 [KO:K03355]
ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
CDC20; cell division cycle 20 [KO:K03363]
PTTG1; pituitary tumor-transforming 1 [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; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:]
BUB3; BUB3 mitotic checkpoint protein [KO:K02180]
BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:]
MAD1L1; MAD1 mitotic arrest deficient-like 1 (yeast) [KO:K06638]
mitotic spindle assembly checkpoint protein MAD2A-like; K02537 mitotic spindle assembly checkpoint protein MAD2 [KO:K02537]
MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
FZR1; fizzy/cell division cycle 20 related 1 (Drosophila) [KO:K03364]
fizzy-related protein homolog; K03364 cell division cycle 20-like protein 1, cofactor of APC complex [KO:K03364]
CDC14B; cell division cycle 14B [KO:K06639] [EC:]
CDC14A; cell division cycle 14A [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:]
CHEK2; checkpoint kinase 2 [KO:K06641] [EC:]
EP300; E1A binding protein p300 [KO:K04498] [EC:]
CREBBP; CREB binding protein [KO:K04498] [EC:]
PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:]
MDM2; MDM2 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:]
growth arrest and DNA damage-inducible protein GADD45 gamma-like; K04402 growth arrest and DNA-damage-inducible protein [KO:K04402]
GADD45A; growth arrest and DNA-damage-inducible, alpha [KO:K04402]
GADD45B; growth arrest and DNA-damage-inducible, beta [KO:K04402]
PCNA; proliferating cell nuclear antigen [KO:K04802]
SFN; stratifin [KO:K06644]
CDC25A; cell division cycle 25A [KO:K06645] [EC:]
ORC1; origin recognition complex, subunit 1 [KO:K02603]
ORC2; origin recognition complex, subunit 2 [KO:K02604]
ORC3; origin recognition complex, subunit 3 [KO:K02605]
ORC4; origin recognition complex, subunit 4 [KO:K02606]
ORC5; origin recognition complex, subunit 5 [KO:K02607]
ORC6; origin recognition complex, subunit 6 [KO:K02608]
MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:]
MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:]
MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:]
MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:]
MCM6; minichromosome maintenance complex component 6 [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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