KEGG   PATHWAY: clud04110
Entry
clud04110                   Pathway                                
Name
Cell cycle - Canis lupus dingo (dingo)
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
clud04110  Cell cycle
clud04110

Other DBs
GO: 0000278
Organism
Canis lupus dingo (dingo) [GN:clud]
Gene
112663184  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
112669048  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
112641579  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
112677962  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
112654545  LOW QUALITY PROTEIN: cyclin-dependent kinase 4-like [KO:K02089] [EC:2.7.11.22]
112674930  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
112678896  RB1; retinoblastoma-associated protein isoform X2 [KO:K06618]
112673913  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
112660467  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
112677338  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
112658381  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
112659842  HDAC1; histone deacetylase 1 isoform X2 [KO:K06067] [EC:3.5.1.98]
112673817  E2F1; transcription factor E2F1 isoform X2 [KO:K17454]
112660192  E2F2; transcription factor E2F2 [KO:K09389]
112657478  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
112646477  E2F4; transcription factor E2F4 [KO:K04682]
112650680  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
112655888  TFDP1; transcription factor Dp-1 isoform X3 [KO:K04683]
112661205  TFDP2; transcription factor Dp-2 isoform X6 [KO:K09392]
112677588  GSK3B; glycogen synthase kinase-3 beta isoform X3 [KO:K03083] [EC:2.7.11.26]
112645426  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
112643136  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
112657820  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
112647773  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
112675712  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
112644105  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
112662261  MYC; myc proto-oncogene protein [KO:K04377]
112659933  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X3 [KO:K10500]
112649891  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
112642487  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
112666506  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
112665406  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112663213  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
112641497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112645606  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
112650816  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
112678040  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
112650539  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
112659018  S-phase kinase-associated protein 1-like [KO:K03094]
112664262  S-phase kinase-associated protein 1-like [KO:K03094]
112651078  CUL1; cullin-1 [KO:K03347]
112667276  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
112652849  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
112669397  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
112642738  CCNA2; cyclin-A2 [KO:K06627]
112655284  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
112646822  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
112642461  ORC1; LOW QUALITY PROTEIN: origin recognition complex subunit 1 [KO:K02603]
112656299  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
112658343  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
112649432  ORC4; origin recognition complex subunit 4 [KO:K02606]
112661261  ORC5; origin recognition complex subunit 5 isoform X2 [KO:K02607]
112642445  ORC6; origin recognition complex subunit 6 isoform X3 [KO:K02608]
112660487  MCM2; DNA replication licensing factor MCM2 isoform X1 [KO:K02540] [EC:5.6.2.3]
112641737  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
112678419  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
112668763  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
112648756  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
112646255  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
112676978  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
112653243  TICRR; treslin isoform X1 [KO:K26117]
112662022  mdm2-binding protein isoform X1 [KO:K26116]
112640889  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
112674988  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
112655121  DBF4B; LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
112651419  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
112660631  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
125753218  G2/mitotic-specific cyclin-B1 [KO:K05868]
112675843  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
112673104  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
112673655  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
112649793  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
112671427  14-3-3 protein theta-like [KO:K16197]
112661983  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
112674006  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
112664855  YWHAQ; 14-3-3 protein theta [KO:K16197]
112654641  LOW QUALITY PROTEIN: 14-3-3 protein zeta/delta-like [KO:K16197]
112661372  14-3-3 protein zeta/delta-like [KO:K16197]
112671739  14-3-3 protein theta-like [KO:K16197]
112665948  14-3-3 protein zeta/delta-like [KO:K16197]
112677584  YWHAE; 14-3-3 protein epsilon isoform X4 [KO:K06630]
112648525  LOW QUALITY PROTEIN: 14-3-3 protein epsilon-like [KO:K06630]
112646175  YWHAG; 14-3-3 protein gamma [KO:K16198]
112676845  YWHAH; 14-3-3 protein eta [KO:K16198]
112649868  14-3-3 protein gamma [KO:K16198]
112640234  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
112667611  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
112650995  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
112640499  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
112653255  CCNH; cyclin-H isoform X1 [KO:K06634]
112660268  CDK7; cyclin-dependent kinase 7 isoform X4 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
112664410  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
112677486  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
112652906  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
112653250  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
112676514  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
112655831  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
112676526  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
112650552  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
112654775  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
112672951  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
112649773  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
112660966  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
112645804  anaphase-promoting complex subunit 13-like [KO:K12456]
112653569  anaphase-promoting complex subunit 13-like [KO:K12456]
112667477  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
118352615  anaphase-promoting complex subunit 15 [KO:K25228]
112651505  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
112642642  CDC20; cell division cycle protein 20 homolog [KO:K03363]
112651682  PTTG1; securin isoform X2 [KO:K06635]
112667190  ESPL1; LOW QUALITY PROTEIN: separin [KO:K02365] [EC:3.4.22.49]
112673071  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
112674805  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
112672326  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
112662051  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
112649050  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
112661124  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
112651909  cohesin subunit SA-2-like [KO:K06671]
112671882  ATRX; transcriptional regulator ATRX isoform X3 [KO:K10779]
112669017  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
112652811  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
112666784  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
112671845  HDAC8; histone deacetylase 8 isoform X3 [KO:K11405] [EC:3.5.1.98]
112669690  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
112647977  ESCO1; N-acetyltransferase ESCO1 isoform X2 [KO:K11268] [EC:2.3.1.-]
125753347  LOW QUALITY PROTEIN: N-acetyltransferase ESCO2-like [KO:K11268] [EC:2.3.1.-]
112669428  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X5 [KO:K11267]
112654091  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
112651209  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
112659245  CDCA5; sororin isoform X1 [KO:K17390]
112647402  AURKB; aurora kinase B isoform X2 [KO:K11479] [EC:2.7.11.1]
112644927  aurora kinase B-like [KO:K11479] [EC:2.7.11.1]
112661116  SGO1; shugoshin 1 [KO:K11580]
112649885  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
112643039  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
112671356  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
112643382  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
112657077  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
112657523  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
112659327  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
112648383  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
112641606  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
112648005  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
112676111  KNL1; kinetochore scaffold 1 isoform X2 [KO:K11542]
112658377  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
112640191  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X6 [KO:K06679]
112659300  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
112678111  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
112676132  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X2 [KO:K06637] [EC:2.7.11.1]
112672457  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
112664421  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
112662730  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
112641640  MAD2L1-binding protein [KO:K26093]
112666270  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
112644320  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
112644579  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
112640776  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
112667202  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
112640446  CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
112678418  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
112660963  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
112671393  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
112677878  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
112647438  TP53; cellular tumor antigen p53 [KO:K04451]
112644859  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112641088  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112666236  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112673637  PCNA; proliferating cell nuclear antigen isoform X1 [KO:K04802]
112659872  SFN; 14-3-3 protein sigma [KO:K06644]
112671112  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
112676766  CHEK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
112665734  CDC25A; M-phase inducer phosphatase 1 isoform X1 [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
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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.
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Cell 75:779-90 (1993)
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Reference
PMID:16936746
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Macaluso M, Montanari M, Giordano A
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Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes.
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Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
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Cobrinik D
  Title
Pocket proteins and cell cycle control.
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Oncogene 24:2796-809 (2005)
DOI:10.1038/sj.onc.1208619
Reference
PMID:17568790
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Boutros R, Lobjois V, Ducommun B
  Title
CDC25 phosphatases in cancer cells: key players? Good targets?
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Nat Rev Cancer 7:495-507 (2007)
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Reference
PMID:9832503
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Diehl JA, Cheng M, Roussel MF, Sherr CJ
  Title
Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.
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Genes Dev 12:3499-511 (1998)
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Reference
PMID:19020303
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Klein EA, Assoian RK
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Transcriptional regulation of the cyclin D1 gene at a glance.
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J Cell Sci 121:3853-7 (2008)
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Reference
PMID:10385618
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Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
DOI:10.1101/gad.13.12.1501
Reference
PMID:12809600
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Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
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Cell 113:685-700 (2003)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:12925736
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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.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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Reference
PMID:16212951
  Authors
Bond M, Sala-Newby GB, Wu YJ, Newby AC
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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)
DOI:10.1016/j.cardiores.2005.08.020
Reference
PMID:15838523
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Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11099028
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Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
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Nature 408:307-10 (2000)
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Reference
PMID:7973727
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Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
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Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
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Science 266:1376-80 (1994)
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Reference
PMID:9889196
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Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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EMBO J 18:396-410 (1999)
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Reference
PMID:17018296
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Sheu YJ, Stillman B
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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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Reference
PMID:9029154
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Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M
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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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EMBO J 16:343-54 (1997)
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Reference
PMID:15876871
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  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)
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Reference
PMID:17426725
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
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Nat Rev Mol Cell Biol 8:379-93 (2007)
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Reference
PMID:12573239
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Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
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Curr Biol 13:R104-14 (2003)
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Reference
PMID:15568976
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Stegmeier F, Amon A
  Title
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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Reference
PMID:9618481
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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.
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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.
  Journal
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
clud03030  DNA replication
clud04010  MAPK signaling pathway
clud04120  Ubiquitin mediated proteolysis
clud04210  Apoptosis
KO pathway
ko04110   
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