KEGG   PATHWAY: nnt04110
Entry
nnt04110                    Pathway                                
Name
Cell cycle - Nestor notabilis (Kea)
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
nnt04110  Cell cycle
nnt04110

Other DBs
GO: 0000278
Organism
Nestor notabilis (Kea) [GN:nnt]
Gene
104410574  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
104407973  LOW QUALITY PROTEIN: G1/S-specific cyclin-D3-like [KO:K10152]
104412454  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104402086  RB1; retinoblastoma-associated protein [KO:K06618]
104407726  RBL1; retinoblastoma-like protein 1 [KO:K04681]
104401950  RBL2; retinoblastoma-like protein 2 [KO:K16332]
104403215  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
104405223  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
104400254  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
104403541  LOW QUALITY PROTEIN: transcription factor E2F2-like [KO:K09389]
104413196  E2F3; transcription factor E2F3 [KO:K06620]
104400312  E2F5; transcription factor E2F5 [KO:K04682]
104402510  E2F4; transcription factor E2F4 [KO:K04682]
104400570  TFDP1; transcription factor Dp-1 [KO:K04683]
104412967  TFDP2; transcription factor Dp-2 [KO:K09392]
104409483  glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
104408091  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
104411056  TGFB3; transforming growth factor beta-3 [KO:K13377]
104399512  mothers against decapentaplegic homolog 2 [KO:K04500]
104410023  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
104407820  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
104403534  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
104401887  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104407470  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
104399884  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
104410084  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
104402769  CUL1; cullin-1 [KO:K03347]
104399424  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
104402803  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
104405909  CCNA1; cyclin-A1 [KO:K06627]
104399652  CCNA2; cyclin-A2 [KO:K06627]
104408945  CDC6; cell division control protein 6 homolog [KO:K02213]
104406882  CDT1; LOW QUALITY PROTEIN: DNA replication factor Cdt1 [KO:K10727]
104408374  ORC1; origin recognition complex subunit 1 [KO:K02603]
104403850  ORC2; LOW QUALITY PROTEIN: origin recognition complex subunit 2 [KO:K02604]
104409571  ORC3; origin recognition complex subunit 3 [KO:K02605]
104407933  LOW QUALITY PROTEIN: origin recognition complex subunit 4-like [KO:K02606]
104403695  ORC5; origin recognition complex subunit 5 [KO:K02607]
104407147  ORC6; origin recognition complex subunit 6 [KO:K02608]
104399810  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
104408972  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
104399158  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
104411755  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
104411668  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
104399099  CDC45; cell division control protein 45 homolog [KO:K06628]
104404309  TICRR; treslin [KO:K26117]
104407855  MTBP; mdm2-binding protein [KO:K26116]
104406138  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
104403575  DBF4; protein DBF4 homolog A [KO:K06629]
104400646  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
104400161  G2/mitotic-specific cyclin-B1-like [KO:K05868]
104410076  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
104400681  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
104401060  14-3-3 protein zeta-like [KO:K16197]
104411623  YWHAQ; 14-3-3 protein theta [KO:K16197]
104406111  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104412916  YWHAH; 14-3-3 protein eta [KO:K16198]
104400551  YWHAG; 14-3-3 protein gamma [KO:K16198]
104406013  PLK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
104400560  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
104400118  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
104399364  CCNH; cyclin-H [KO:K06634]
104408890  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
104405604  LOW QUALITY PROTEIN: anaphase-promoting complex subunit 1-like [KO:K03348]
104410823  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
104411981  CDC27; LOW QUALITY PROTEIN: cell division cycle protein 27 homolog [KO:K03350]
104411596  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
104409454  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
104399578  CDC16; cell division cycle protein 16 homolog [KO:K03353]
104409561  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
104399063  CDC23; cell division cycle protein 23 homolog [KO:K03355]
104404687  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
104399024  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
104404277  ANAPC16; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 16 [KO:K25229]
104407634  CDC20; cell division cycle protein 20 homolog [KO:K03363]
104408348  PTTG1; securin [KO:K06635]
104399238  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
104410375  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
104405854  RAD21; LOW QUALITY PROTEIN: double-strand-break repair protein rad21 homolog [KO:K06670]
104403074  cohesin subunit SA-2-like [KO:K06671]
104403877  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
104405724  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
104406556  ATRX; LOW QUALITY PROTEIN: transcriptional regulator ATRX [KO:K10779]
104404036  DDX11; probable ATP-dependent RNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
104407530  nipped-B-like protein [KO:K06672]
104399464  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
104399442  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
104404560  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
104402081  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
104410040  PDS5A; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
104399179  sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
104411921  WAPAL; wings apart-like protein homolog [KO:K25163]
104403638  SGOL1; shugoshin-like 1 [KO:K11580]
104400446  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104400981  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
104403421  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
104408235  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
104400170  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform-like [KO:K11584]
104401786  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
104399549  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
104405146  CASC5; protein CASC5 [KO:K11542]
104409660  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
104399128  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
104410793  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
104406410  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
104409079  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
104406949  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
104399793  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
104406839  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
104407240  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
104412878  FBXO5; F-box only protein 5 [KO:K10292]
104407611  dual specificity protein phosphatase CDC14B-like [KO:K06639] [EC:3.1.3.16 3.1.3.48]
104407743  dual specificity protein phosphatase CDC14A-like [KO:K06639] [EC:3.1.3.16 3.1.3.48]
104401705  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
104406465  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104402397  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
104399280  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
104410320  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
104410537  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104401002  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104400634  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
104410411  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104409840  PCNA; proliferating cell nuclear antigen [KO:K04802]
104400295  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
104400160  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
104406434  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
nnt03030  DNA replication
nnt04010  MAPK signaling pathway
nnt04120  Ubiquitin mediated proteolysis
nnt04210  Apoptosis
KO pathway
ko04110   
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