KEGG   PATHWAY: mdo04110
Entry
mdo04110                    Pathway                                
Name
Cell cycle - Monodelphis domestica (gray short-tailed 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
Pathway map
mdo04110  Cell cycle
mdo04110

Other DBs
GO: 0000278
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100013257  CCND1; cyclin D1 [KO:K04503]
100016259  CCND2; cyclin D2 [KO:K10151]
100027538  CCND3; cyclin D3 [KO:K10152]
100021675  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100022630  RB1; RB transcriptional corepressor 1 [KO:K06618]
100029326  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
100019136  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
100619549  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
100022756  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100032301  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100032280  E2F1; E2F transcription factor 1 [KO:K17454]
100009746  E2F2; E2F transcription factor 2 [KO:K09389]
100017977  E2F3; E2F transcription factor 3 [KO:K06620]
100020064  E2F4; E2F transcription factor 4 [KO:K04682]
100026008  E2F5; E2F transcription factor 5 [KO:K04682]
100021442  TFDP1; transcription factor Dp-1 [KO:K04683]
100618187  TFDP2; transcription factor Dp-2 [KO:K09392]
100012447  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100019183  TGFB1; transforming growth factor beta 1 [KO:K13375]
100017548  TGFB2; transforming growth factor beta 2 [KO:K13376]
100017937  TGFB3; transforming growth factor beta 3 [KO:K13377]
100014493  SMAD2; SMAD family member 2 [KO:K04500]
100018703  SMAD3; SMAD family member 3 [KO:K23605]
100010143  SMAD4; SMAD family member 4 [KO:K04501]
100032344  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100619919  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
554242  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
100021947  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
100020812  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
100012509  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
100014923  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
100029103  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
100014623  CCNE1; cyclin E1 [KO:K06626]
100022654  CCNE2; cyclin E2 [KO:K06626]
100030421  G1/S-specific cyclin-E2-like [KO:K06626]
100014810  SKP1; S-phase kinase associated protein 1 [KO:K03094]
100013348  CUL1; cullin 1 [KO:K03347]
100013521  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
100020421  SKP2; S-phase kinase associated protein 2 [KO:K03875]
100017104  CCNA2; cyclin A2 [KO:K06627]
100027136  CCNA1; cyclin A1 [KO:K06627]
100016182  CDC6; cell division cycle 6 [KO:K02213]
100026231  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
100018853  ORC1; origin recognition complex subunit 1 [KO:K02603]
100016693  ORC2; origin recognition complex subunit 2 [KO:K02604]
100025381  ORC3; origin recognition complex subunit 3 [KO:K02605]
100013255  ORC4; origin recognition complex subunit 4 [KO:K02606]
100018063  ORC5; origin recognition complex subunit 5 [KO:K02607]
100015843  ORC6; origin recognition complex subunit 6 [KO:K02608]
100027730  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
100013668  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
100030676  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
100016494  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
100012357  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
100018145  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
100029459  CDC45; cell division cycle 45 [KO:K06628]
100617454  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
100031920  MTBP; MDM2 binding protein [KO:K26116]
100015595  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
100027385  DBF4; DBF4 zinc finger [KO:K06629]
100023607  DBF4B; DBF4 zinc finger B [KO:K06629]
100019039  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100019387  CCNB1; cyclin B1 [KO:K05868]
100019727  CCNB2; cyclin B2 [KO:K21770]
100020720  CCNB3; cyclin B3 [KO:K21771]
100025023  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
100014440  M-phase inducer phosphatase 3-like [KO:K05867] [EC:3.1.3.48]
100030704  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
100024059  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
100032061  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100012276  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
100016805  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
100029105  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
100027403  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
100021160  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
100024283  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
100618653  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
100011386  CCNH; cyclin H [KO:K06634]
100019498  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100031108  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
100023440  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
100025278  CDC27; cell division cycle 27 [KO:K03350]
100012855  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
100015868  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
100016016  CDC16; cell division cycle 16 [KO:K03353]
100020392  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
100024960  CDC23; cell division cycle 23 [KO:K03355]
100019010  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
100025534  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
100016215  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
100013043  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
100009794  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
100030438  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
100032809  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
100028429  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
100009927  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
100021816  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
100025333  RAD21; RAD21 cohesin complex component [KO:K06670]
100016681  STAG2; stromal antigen 2 [KO:K06671]
100023927  STAG1; stromal antigen 1 [KO:K06671]
100011334  cohesin subunit SA-2-like [KO:K06671]
100019492  ATRX; ATRX, chromatin remodeler [KO:K10779]
100020572  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
100014459  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
100011955  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
100618462  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
100030510  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
100013062  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
100028093  N-acetyltransferase ESCO2-like [KO:K11268] [EC:2.3.1.-]
100021782  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
100020670  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
100013552  WAPL; WAPL cohesin release factor [KO:K25163]
100030607  CDCA5; cell division cycle associated 5 [KO:K17390]
100014142  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
100031201  SGO1; shugoshin 1 [KO:K11580]
100012652  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
100017519  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
100026516  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
100028805  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
100017824  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
100010758  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
100022186  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
100016488  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
100011983  NDC80; NDC80, kinetochore complex component [KO:K11547]
100032004  KNL1; kinetochore scaffold 1 [KO:K11542]
100023737  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
100029239  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
100018245  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
100013798  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
100019351  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
100033212  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
100014792  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
100012045  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
100010404  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
100027495  fizzy-related protein homolog [KO:K03364]
100032184  FBXO5; F-box protein 5 [KO:K10292]
100011309  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100029604  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100619552  dual specificity protein phosphatase CDC14C-like [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100028102  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
100013876  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
100030684  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
100019691  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
100026797  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
100021398  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103092862  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
497248  TP53; tumor protein p53 [KO:K04451]
100010225  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
100016952  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
100014651  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
100029293  PCNA; proliferating cell nuclear antigen [KO:K04802]
100012611  SFN; stratifin [KO:K06644]
100016170  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
100030584  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
100018150  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
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
mdo03030  DNA replication
mdo04010  MAPK signaling pathway
mdo04120  Ubiquitin mediated proteolysis
mdo04210  Apoptosis
KO pathway
ko04110   
LinkDB

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