KEGG   PATHWAY: mdo04110Help
Entry
mdo04110                    Pathway                                

Name
Cell cycle - Monodelphis domestica (opossum)
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
mdo04110

All organismsOrtholog table
Module
Origin recognition complex [PATH:mdo04110]
MCM complex [PATH:mdo04110]
DNA-PK complex [PATH:mdo04110]
SCF-SKP2 complex [PATH:mdo04110]
APC/C complex [PATH:mdo04110]
Other DBs
BSID: 
GO: 
Organism
Monodelphis domestica (opossum) [GN:mdo]
Gene
CCND1; cyclin D1 [KO:K04503]
CCND2; cyclin D2 [KO:K10151]
CCND3; cyclin D3 [KO:K10152]
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
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:2.7.10.2]
HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
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:2.7.11.26]
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:2.7.11.1]
DBF4; DBF4 zinc finger [KO:K06629]
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
CCNB1; cyclin B1 [KO:K05868]
CCNB2; cyclin B2 [KO:K05868]
CCNB3; cyclin B3 [KO:K05868]
CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
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:2.7.11.21]
WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
WEE2; WEE1 homolog 2 (S. pombe) [KO:K06632] [EC:2.7.11.1]
PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
CCNH; cyclin H [KO:K06634]
CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.23 2.7.11.22]
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:3.4.22.49]
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:2.7.12.1]
BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
BUB3; BUB3 mitotic checkpoint protein [KO:K02180]
BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
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:3.1.3.48 3.1.3.16]
CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.48 3.1.3.16]
ATR; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
ATM; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
497248  
TP53; tumor protein p53 [KO:K04451]
CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
MDM2; MDM2 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
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:3.1.3.48]
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:3.6.4.12]
MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:3.6.4.12]
MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:3.6.4.12]
MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:3.6.4.12]
MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:3.6.4.12]
MCM7; 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)
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