KEGG   PATHWAY: aful04110
Entry
aful04110                   Pathway                                
Name
Cell cycle - Aythya fuligula (tufted duck)
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
aful04110  Cell cycle
aful04110

Other DBs
GO: 0000278
Organism
Aythya fuligula (tufted duck) [GN:aful]
Gene
116490240  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
116494310  CCND2; LOW QUALITY PROTEIN: G1/S-specific cyclin-D2 [KO:K10151]
116498945  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
116485812  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
116496385  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
116495748  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
116493890  RBL2; retinoblastoma-like protein 2 [KO:K16332]
116496816  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
116487709  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
116498169  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
116495793  E2F1; transcription factor E2F1 [KO:K17454]
116498201  transcription factor E2F2-like [KO:K09389]
116486676  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
116494212  E2F4; transcription factor E2F4 [KO:K04682]
116486041  E2F5; transcription factor E2F5 [KO:K04682]
116501772  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
116492293  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
116494482  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116488326  TGFB2; LOW QUALITY PROTEIN: transforming growth factor beta-2 proprotein [KO:K13376]
116490182  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
116500445  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
116493384  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
116499524  mothers against decapentaplegic homolog 4-like [KO:K04501]
116500438  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
116486166  MYC; myc proto-oncogene protein [KO:K04377]
116497488  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
116500967  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
116500968  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
116492049  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
116501761  CDKN1B; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1B [KO:K06624]
116489798  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
116498917  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
116488021  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
116494126  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
116486032  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
116499925  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
116494750  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
116486424  CUL1; cullin-1 [KO:K03347]
116501779  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
116500511  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
116493586  CCNA1; cyclin-A1 [KO:K06627]
116488737  CCNA2; cyclin-A2 [KO:K06627]
116498275  CDC6; LOW QUALITY PROTEIN: cell division control protein 6 homolog [KO:K02213]
116493954  CDT1; DNA replication factor Cdt1 [KO:K10727]
116491675  ORC1; origin recognition complex subunit 1 [KO:K02603]
116490443  ORC2; origin recognition complex subunit 2 [KO:K02604]
116488193  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
116490813  ORC4; origin recognition complex subunit 4 [KO:K02606]
116502408  ORC5; origin recognition complex subunit 5 [KO:K02607]
116493906  ORC6; origin recognition complex subunit 6 [KO:K02608]
116493265  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
116488352  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
116486480  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
116495453  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
116490926  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
116496099  CDC45; cell division control protein 45 homolog [KO:K06628]
116493537  TICRR; treslin [KO:K26117]
116486008  MTBP; mdm2-binding protein [KO:K26116]
116491674  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
116498325  DBF4B; protein DBF4 homolog B [KO:K06629]
116486739  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
116491620  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
116493403  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
116494608  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
116487422  YWHAQ; 14-3-3 protein theta [KO:K16197]
116495583  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
116485883  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
116497333  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
116496005  YWHAH; 14-3-3 protein eta [KO:K16198]
116497122  YWHAG; 14-3-3 protein gamma [KO:K16198]
116495259  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
116501852  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
116489809  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
116501129  CCNH; cyclin-H [KO:K06634]
116500810  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
116487346  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
116496789  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
116498373  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
116489186  ANAPC4; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 4 [KO:K03351]
116496269  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
116499087  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
116496263  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
116494753  CDC23; cell division cycle protein 23 homolog [KO:K03355]
116488786  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
116496557  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
116496803  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
116492596  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
116493576  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
116491236  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
116491967  CDC20; cell division cycle protein 20 homolog [KO:K03363]
116494998  PTTG1; securin [KO:K06635]
116501724  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
116488471  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
116491321  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
116485956  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
116492603  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
116494273  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
116490372  cohesin subunit SA-2-like isoform X1 [KO:K06671]
116494305  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
116502073  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
116500453  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
116501380  nipped-B-like protein isoform X1 [KO:K06672]
116499237  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
116494623  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
116486910  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
116487781  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
116488683  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
116489816  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
116491437  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
116486840  SGO1; shugoshin 1 [KO:K11580]
116488752  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
116494731  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
116487114  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
116487368  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
116489434  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
116489604  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
116486667  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
116490274  KNL1; kinetochore scaffold 1 [KO:K11542]
116488242  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
116495187  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
116488811  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
116497616  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
116490236  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
116491593  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
116488338  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
116486462  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
116487670  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
116499155  FZR1; fizzy-related protein homolog [KO:K03364]
116487694  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
116500452  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116491762  CDC14A; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116488293  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
116495102  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116485633  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
116492555  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
116490910  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
116486905  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
116492040  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116500801  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116499467  PCNA; proliferating cell nuclear antigen [KO:K04802]
116498122  SFN; 14-3-3 protein sigma [KO:K06644]
116497895  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
116496237  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
116486619  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
aful03030  DNA replication
aful04010  MAPK signaling pathway
aful04120  Ubiquitin mediated proteolysis
aful04210  Apoptosis
KO pathway
ko04110   
LinkDB

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