KEGG   PATHWAY: cata04110
Entry
cata04110                   Pathway                                
Name
Cell cycle - Cygnus atratus (black swan)
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
cata04110  Cell cycle
cata04110

Other DBs
GO: 0000278
Organism
Cygnus atratus (black swan) [GN:cata]
Gene
118250840  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
118247742  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
118255260  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
118247522  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
118251390  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
118248807  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
118246311  RBL2; retinoblastoma-like protein 2 [KO:K16332]
118252285  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
118255705  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
118244085  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
118248968  E2F1; transcription factor E2F1 [KO:K17454]
118255672  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
118249682  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
118247961  E2F5; transcription factor E2F5 [KO:K04682]
118246283  E2F4; transcription factor E2F4 [KO:K04682]
118257499  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
118247273  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
118244932  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118253345  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
118244426  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
118254572  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118259701  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118254640  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
118258600  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4-like [KO:K04501]
118252717  MYC; LOW QUALITY PROTEIN: myc proto-oncogene protein [KO:K04377]
118258837  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
118256258  cyclin-dependent kinase 4 inhibitor B-like isoform X1 [KO:K04685]
118256259  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
118243474  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
118250192  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
118244525  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
118260390  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
118250064  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1-like [KO:K06625]
118247930  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
118246303  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
118261013  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
118254958  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
118250932  CUL1; cullin-1 [KO:K03347]
118250500  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
118256634  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
118250404  CCNA2; cyclin-A2 [KO:K06627]
118246070  CCNA1; cyclin-A1 [KO:K06627]
118257827  CDT1; DNA replication factor Cdt1 [KO:K10727]
118243763  ORC1; LOW QUALITY PROTEIN: origin recognition complex subunit 1 [KO:K02603]
118254305  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
118252578  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
118249527  ORC5; origin recognition complex subunit 5 [KO:K02607]
118246332  ORC6; origin recognition complex subunit 6 [KO:K02608]
118248227  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
118256604  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
118251230  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
118250655  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
118252657  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
118252917  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
118251949  TICRR; treslin [KO:K26117]
118252703  MTBP; mdm2-binding protein isoform X2 [KO:K26116]
118243699  CDC7; LOW QUALITY PROTEIN: cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
118247487  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
118258302  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
118245775  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
118251456  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
118251724  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
118261102  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
118247943  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
118249010  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
118246148  YWHAQ; 14-3-3 protein theta [KO:K16197]
118254053  YWHAE; 14-3-3 protein epsilon [KO:K06630]
118254163  YWHAG; 14-3-3 protein gamma [KO:K16198]
118252925  YWHAH; 14-3-3 protein eta [KO:K16198]
118256462  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
118249783  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
118259215  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
118256326  CCNH; cyclin-H isoform X1 [KO:K06634]
118251442  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
118257425  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
118257054  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
118258891  CDC27; cell division cycle protein 27 homolog isoform X2 [KO:K03350]
118248432  ANAPC4; anaphase-promoting complex subunit 4 isoform X2 [KO:K03351]
118257238  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
118257483  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
118257250  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
118254858  CDC23; cell division cycle protein 23 homolog [KO:K03355]
118249462  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
118257092  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
118247079  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
118243504  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
118243711  CDC20; cell division cycle protein 20 homolog [KO:K03363]
118256730  PTTG1; securin [KO:K06635]
118261562  ESPL1; LOW QUALITY PROTEIN: separin [KO:K02365] [EC:3.4.22.49]
118250061  SMC1B; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1B [KO:K06636]
118248540  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
118252662  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
118253587  cohesin subunit SA-2-like isoform X1 [KO:K06671]
118247003  STAG1; LOW QUALITY PROTEIN: cohesin subunit SA-1 [KO:K06671]
118245338  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
118245532  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
118250143  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
118256627  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
118259900  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
118245401  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
118256806  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
118259075  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
118250453  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
118245999  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
118260296  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
118252788  SGO1; shugoshin 1 [KO:K11580]
118254959  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118259190  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
118250210  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
118250269  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118252771  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
118252915  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
118256763  NDC80; kinetochore protein NDC80 homolog isoform X2 [KO:K11547]
118244783  KNL1; kinetochore scaffold 1 [KO:K11542]
118254339  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
118249369  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
118250365  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
118253383  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
118244678  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
118248669  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
118257429  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
118259378  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
118254321  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
118259007  FZR1; fizzy-related protein homolog [KO:K03364]
118244101  FBXO5; F-box only protein 5 isoform X2 [KO:K10292]
118243303  CDC14A; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
118257357  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
118249299  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
118250506  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
118251234  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
118246943  ATR; serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
118245849  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
118246834  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
118259579  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
118260854  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
118256951  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
118259352  PCNA; proliferating cell nuclear antigen [KO:K04802]
118255828  SFN; 14-3-3 protein sigma [KO:K06644]
118252468  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
118257551  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
118251873  CDC25A; M-phase inducer phosphatase 1 [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
cata03030  DNA replication
cata04010  MAPK signaling pathway
cata04120  Ubiquitin mediated proteolysis
cata04210  Apoptosis
KO pathway
ko04110   
LinkDB

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