KEGG   PATHWAY: gas04110
Entry
gas04110                    Pathway                                
Name
Cell cycle - Gracilinanus agilis (agile gracile 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
gas04110  Cell cycle
gas04110

Other DBs
GO: 0000278
Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123250729  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123245608  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123251284  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123249650  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
123240551  RB1; retinoblastoma-associated protein [KO:K06618]
123237411  RBL1; retinoblastoma-like protein 1 [KO:K04681]
123237309  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
123237223  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
123247757  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
123256336  LOW QUALITY PROTEIN: histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
123240434  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
123235468  E2F1; transcription factor E2F1 [KO:K17454]
123240067  E2F3; transcription factor E2F3 [KO:K06620]
123238314  E2F5; transcription factor E2F5 [KO:K04682]
123234651  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
123242608  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
123242773  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
123242376  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123256028  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123247856  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
123235863  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123237729  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
123238038  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
123253784  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4-like [KO:K04501]
123254358  mothers against decapentaplegic homolog 4-like [KO:K04501]
123237642  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
123241543  MYC; myc proto-oncogene protein [KO:K04377]
123240337  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
123231247  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
123231248  cyclin-dependent kinase inhibitor 2A [KO:K04685]
123245033  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
123242274  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
123248489  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
123243800  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123235321  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123251985  G1/S-specific cyclin-E2-like [KO:K06626]
123246605  G1/S-specific cyclin-E2-like [KO:K06626]
123240740  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
123248961  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123235711  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
123251960  S-phase kinase-associated protein 1-like [KO:K03094]
123249675  CUL1; cullin-1 [KO:K03347]
123250747  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
123231512  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
123241261  CCNA1; cyclin-A1 [KO:K06627]
123233185  cyclin-A2-like [KO:K06627]
123233186  cyclin-A2-like [KO:K06627]
123233190  cyclin-A2-like [KO:K06627]
123233191  cyclin-A2-like [KO:K06627]
123251689  CCNA2; cyclin-A2 [KO:K06627]
123240765  cyclin-A2-like [KO:K06627]
123245206  CDC6; cell division control protein 6 homolog [KO:K02213]
123236767  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
123245476  ORC1; origin recognition complex subunit 1 [KO:K02603]
123241892  ORC2; origin recognition complex subunit 2 [KO:K02604]
123247471  ORC3; origin recognition complex subunit 3 [KO:K02605]
123242270  ORC4; origin recognition complex subunit 4 [KO:K02606]
123248962  ORC5; origin recognition complex subunit 5 [KO:K02607]
123235312  ORC6; origin recognition complex subunit 6 [KO:K02608]
123247323  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
123244778  MCM3; LOW QUALITY PROTEIN: DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
123231722  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
123248887  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
123239334  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
123244893  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
123230426  CDC45; cell division control protein 45 homolog [KO:K06628]
123236195  TICRR; treslin [KO:K26117]
123231947  mdm2-binding protein [KO:K26116]
123244203  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
123249360  LOW QUALITY PROTEIN: protein DBF4 homolog A-like [KO:K06629]
123250660  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
123236533  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
123251651  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
123236114  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
123234491  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
123233861  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
123235790  YWHAQ; 14-3-3 protein theta [KO:K16197]
123237744  14-3-3 protein zeta/delta-like [KO:K16197]
123245069  14-3-3 protein zeta/delta-like [KO:K16197]
123234719  14-3-3 protein zeta/delta-like [KO:K16197]
123235041  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
123240956  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
123253939  14-3-3 protein epsilon-like [KO:K06630]
123236441  14-3-3 protein epsilon [KO:K06630]
123244438  YWHAE; 14-3-3 protein epsilon [KO:K06630]
123247526  YWHAG; 14-3-3 protein gamma [KO:K16198]
123230419  YWHAH; 14-3-3 protein eta [KO:K16198]
123231080  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
123249916  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
123246238  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
123252527  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
123231533  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
123231407  CCNH; cyclin-H isoform X1 [KO:K06634]
123236862  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
123233395  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
123237183  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
123244567  CDC27; cell division cycle protein 27 homolog [KO:K03350]
123251367  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
123232349  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
123239793  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
123234483  LOW QUALITY PROTEIN: cell division cycle protein 16 homolog [KO:K03353]
123244835  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
123235658  CDC23; cell division cycle protein 23 homolog [KO:K03355]
123251542  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
123247660  anaphase-promoting complex subunit 11-like [KO:K03358]
123243802  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
123237269  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
123239428  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
123240490  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
123232961  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
123244299  CDC20; cell division cycle protein 20 homolog [KO:K03363]
123235568  PTTG1; securin [KO:K06635]
123250223  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
123249268  SMC1B; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1B [KO:K06636]
123249427  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
123238164  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
123231940  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
123253548  STAG2; cohesin subunit SA-2 [KO:K06671]
123241525  STAG1; cohesin subunit SA-1 [KO:K06671]
123242568  cohesin subunit SA-2-like [KO:K06671]
123253640  ATRX; transcriptional regulator ATRX [KO:K10779]
123253803  transcriptional regulator ATRX-like [KO:K10779]
123248892  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
123237417  NIPBL; nipped-B-like protein [KO:K06672]
123243250  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
123242674  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
123239358  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
123235011  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
123251229  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
123240583  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
123233002  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
123252782  CDCA5; LOW QUALITY PROTEIN: sororin [KO:K17390]
123245037  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
123249761  SGO1; shugoshin 1 [KO:K11580]
123237637  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123251011  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123252361  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
123241835  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
123240795  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123237600  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
123237748  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
123232498  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform-like [KO:K11584]
123245114  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
123245668  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
123253965  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
123234080  KNL1; kinetochore scaffold 1 [KO:K11542]
123245221  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
123234029  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
123252874  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
123240310  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
123234086  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
123238208  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
123236932  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
123231570  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
123245255  MAD2L1-binding protein [KO:K26093]
123253581  fizzy-related protein homolog [KO:K03364]
123253934  fizzy-related protein homolog [KO:K03364]
123254801  fizzy-related protein homolog [KO:K03364]
123243162  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
123256686  fizzy-related protein homolog [KO:K03364]
123256693  fizzy-related protein homolog [KO:K03364]
123247791  FBXO5; F-box only protein 5 [KO:K10292]
123235246  CDC14B; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
123243958  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
123231726  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
123250301  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
123253625  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
123241957  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
123241475  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
123248749  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
123251829  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
123244534  TP53; cellular tumor antigen p53 [KO:K04451]
123255768  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
123232226  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123251065  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123234893  PCNA; proliferating cell nuclear antigen [KO:K04802]
123243178  SFN; 14-3-3 protein sigma [KO:K06644]
123238925  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
123256922  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
123230824  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
Reference
PMID:7908906
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Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
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Oncogene 25:5263-7 (2006)
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Oncogene 24:2796-809 (2005)
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PMID:17568790
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CDC25 phosphatases in cancer cells: key players? Good targets?
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Nat Rev Cancer 7:495-507 (2007)
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Cell 113:685-700 (2003)
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Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
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Cardiovasc Res 69:198-206 (2006)
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Reference
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The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
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PMID:11099028
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Surfing the p53 network.
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Nature 408:307-10 (2000)
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Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
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Mol Cell 24:101-13 (2006)
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Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity.
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CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?
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Reference
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The spindle-assembly checkpoint in space and time.
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Chromosome cohesion and separation: from men and molecules.
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Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
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Annu Rev Genet 38:203-32 (2004)
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Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
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Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
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de Boer HR, Guerrero Llobet S, van Vugt MA
  Title
Controlling the response to DNA damage by the APC/C-Cdh1.
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Cell Mol Life Sci 73:949-60 (2016)
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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
gas03030  DNA replication
gas04010  MAPK signaling pathway
gas04120  Ubiquitin mediated proteolysis
gas04210  Apoptosis
KO pathway
ko04110   
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