KEGG   PATHWAY: dnm04110
Entry
dnm04110                    Pathway                                
Name
Cell cycle - Dasypus novemcinctus (nine-banded armadillo)
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
dnm04110  Cell cycle
dnm04110

Other DBs
GO: 0000278
Organism
Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]
Gene
101410694  [KO:K03456]
101411009  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101411123  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101411174  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101411312  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
101411471  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
101411623  ORC5; origin recognition complex subunit 5 [KO:K02607]
101411769  YWHAH; 14-3-3 protein eta [KO:K16198]
101411867  CDC26; anaphase-promoting complex subunit CDC26 isoform X3 [KO:K03359]
101411899  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101411988  [KO:K11268] [EC:2.3.1.-]
101412025  SMC3; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 3 [KO:K06669]
101412267  TFDP1; transcription factor Dp-1 [KO:K04683]
101412555  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
101412803  FZR1; fizzy-related protein homolog [KO:K03364]
101413382  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]
101413410  CDC23; cell division cycle protein 23 homolog [KO:K03355]
101413586  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101413602  KNL1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
101413678  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101414222  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101414715  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
101415205  CUL1; LOW QUALITY PROTEIN: cullin-1 [KO:K03347]
101415802  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
101416069  TP53; cellular tumor antigen p53 [KO:K04451]
101416229  TICRR; treslin [KO:K26117]
101416305  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101416412  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
101416795  MCM4; LOW QUALITY PROTEIN: DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
101417330  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101418100  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101418104  ORC3; origin recognition complex subunit 3 [KO:K02605]
101418416  [KO:K11268] [EC:2.3.1.-]
101418436  [KO:K03354]
101418445  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101418452  STAG1; cohesin subunit SA-1 [KO:K06671]
101418463  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101418742  [KO:K02537]
101418819  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101419119  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
101419182  YWHAQ; 14-3-3 protein theta [KO:K16197]
101419186  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101419231  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101419351  DDX11; ATP-dependent DNA helicase DDX11 isoform X2 [KO:K11273] [EC:3.6.4.13]
101419876  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
101419897  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101420088  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
101420243  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
101420273  RBL1; retinoblastoma-like protein 1 isoform X2 [KO:K04681]
101420312  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
101420469  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
101420648  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101421042  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101421775  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
101421795  E2F3; transcription factor E2F3 [KO:K06620]
101422125  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
101422574  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
101422825  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101423341  YWHAG; 14-3-3 protein gamma [KO:K16198]
101423546  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
101423556  [KO:K06621]
101423665  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
101423936  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101423941  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101424039  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101424184  CDT1; DNA replication factor Cdt1 [KO:K10727]
101424904  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
101424995  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101425169  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101425731  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101425834  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101425904  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101426099  TFDP2; transcription factor Dp-2 isoform X3 [KO:K09392]
101426219  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
101426599  NIPBL; nipped-B-like protein [KO:K06672]
101426707  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101427388  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
101427644  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
101427751  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101427862  SGO1; shugoshin 1 [KO:K11580]
101427870  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101428199  CDC45; cell division control protein 45 homolog [KO:K06628]
101428404  CDC14B; dual specificity protein phosphatase CDC14B isoform X3 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101429090  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101429105  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
101429422  CDC20; cell division cycle protein 20 homolog [KO:K03363]
101429531  CDC16; cell division cycle protein 16 homolog [KO:K03353]
101429626  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
101429916  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101431286  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
101431300  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101431875  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101432095  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101433013  MAD2L1; LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101433274  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
101433313  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
101433564  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101433627  PCNA; proliferating cell nuclear antigen [KO:K04802]
101433652  CDC6; cell division control protein 6 homolog [KO:K02213]
101433906  ATRX; LOW QUALITY PROTEIN: transcriptional regulator ATRX [KO:K10779]
101434076  PTTG1; securin [KO:K06635]
101434268  [KO:K11584]
101434549  TGFB3; transforming growth factor beta-3 [KO:K13377]
101434625  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
101434680  CCNA1; cyclin-A1 [KO:K06627]
101434837  CDC14A; dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101434858  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
101435754  SFN; 14-3-3 protein sigma [KO:K06644]
101437007  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
101437265  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
101437282  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
101437302  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
101437315  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101437375  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101437422  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101437428  ORC6; origin recognition complex subunit 6 [KO:K02608]
101437683  [KO:K03094]
101437737  TGFB1; transforming growth factor beta-1 [KO:K13375]
101437881  ORC4; LOW QUALITY PROTEIN: origin recognition complex subunit 4 [KO:K02606]
101438620  MTBP; mdm2-binding protein [KO:K26116]
101438903  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101438974  [KO:K06635]
101439228  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101439717  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101439768  ESPL1; LOW QUALITY PROTEIN: separin [KO:K02365] [EC:3.4.22.49]
101439842  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
101439951  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
101440377  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
101440414  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101440649  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
101440679  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101440765  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101440851  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101441014  ORC1; origin recognition complex subunit 1 [KO:K02603]
101441195  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101441252  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101441461  CDCA5; sororin [KO:K17390]
101441708  [KO:K06618]
101442203  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
101442624  [KO:K16197]
101443141  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101443474  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
101443494  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101444027  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101444404  DBF4B; LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
101444584  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
101444912  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
101445592  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
101445754  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
101446627  CCNH; cyclin-H [KO:K06634]
101446897  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101447050  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
101447415  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101447966  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
105744121  CCNA2; cyclin-A2 [KO:K06627]
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
dnm03030  DNA replication
dnm04010  MAPK signaling pathway
dnm04120  Ubiquitin mediated proteolysis
dnm04210  Apoptosis
KO pathway
ko04110   

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