KEGG   PATHWAY: pspa04110
Entry
pspa04110                   Pathway                                
Name
Cell cycle - Polyodon spathula (Mississippi paddlefish)
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
pspa04110  Cell cycle
pspa04110

Other DBs
GO: 0000278
Organism
Polyodon spathula (Mississippi paddlefish) [GN:pspa]
Gene
121294289  [KO:K26117]
121294311  [KO:K04402]
121294349  [KO:K05866] [EC:3.1.3.48]
121294513  [KO:K21770]
121294921  [KO:K23605]
121294975  wee1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
121295039  [KO:K09993]
121295125  [KO:K04503]
121295282  [KO:K10779]
121295342  [KO:K21771]
121295442  [KO:K06671]
121295649  [KO:K11405] [EC:3.5.1.98]
121296104  [KO:K06626]
121296191  [KO:K02608]
121296220  cdkn2a/b; cyclin-dependent kinase inhibitor 2A [KO:K04685]
121296548  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
121296603  [KO:K16332]
121296890  cdc45; cell division control protein 45 homolog [KO:K06628]
121296987  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
121297010  cdc23; cell division cycle protein 23 homolog [KO:K03355]
121297208  [KO:K11547]
121297320  [KO:K04382] [EC:3.1.3.16]
121297394  [KO:K16198]
121297530  [KO:K06635]
121297533  [KO:K03354]
121297569  [KO:K06635]
121297582  [KO:K03094]
121297701  [KO:K02540] [EC:5.6.2.3]
121297708  [KO:K17454]
121297932  [KO:K06670]
121297946  [KO:K16197]
121298159  [KO:K04377]
121298657  [KO:K03456]
121298958  [KO:K04685]
121299044  [KO:K21770]
121299241  [KO:K23605]
121299476  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
121299757  [KO:K06625]
121299765  anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
121299920  [KO:K10152]
121299948  [KO:K10152]
121300128  [KO:K11547]
121300130  [KO:K16198]
121300219  [KO:K03354]
121300371  [KO:K06628]
121300671  [KO:K05868]
121300682  [KO:K05868]
121300700  [KO:K04498] [EC:2.3.1.48]
121300751  [KO:K03364]
121300783  [KO:K06631] [EC:2.7.11.21]
121300878  mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
121301031  [KO:K04402]
121301154  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
121301211  [KO:K04498] [EC:2.3.1.48]
121301230  [KO:K11266]
121301532  fzr1a; fizzy/cell division cycle 20 related 1a isoform X1 [KO:K03364]
121301574  [KO:K11266]
121301897  [KO:K03350]
121302100  [KO:K04402]
121302121  [KO:K04402]
121302141  [KO:K04402]
121302355  [KO:K04802]
121302730  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
121302795  pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
121302804  [KO:K06618]
121302918  ccna1; cyclin-A1 [KO:K06627]
121302935  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
121302976  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121303097  [KO:K04802]
121303852  [KO:K04500]
121303981  [KO:K03456]
121304148  [KO:K26117]
121304289  [KO:K04501]
121304409  [KO:K03456]
121304753  [KO:K10152]
121304756  [KO:K06625]
121304766  [KO:K03875]
121304841  [KO:K06672]
121304856  [KO:K21770]
121304906  [KO:K13375]
121305006  [KO:K02202] [EC:2.7.11.22 2.7.11.23]
121305212  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
121305362  [KO:K06636]
121305621  [KO:K11479] [EC:2.7.11.1]
121305661  [KO:K06671]
121305685  [KO:K04451]
121305689  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
121305744  [KO:K11479] [EC:2.7.11.1]
121305898  ccndx; cyclin Dx [KO:K04503]
121306077  [KO:K04498] [EC:2.3.1.48]
121306188  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
121306205  [KO:K06634]
121306333  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
121306334  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
121306517  [KO:K04451]
121306557  [KO:K11479] [EC:2.7.11.1]
121306558  [KO:K11479] [EC:2.7.11.1]
121306659  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
121307598  cdt1; DNA replication factor Cdt1 [KO:K10727]
121307800  [KO:K04681]
121307835  [KO:K04682]
121307857  [KO:K04681]
121307859  [KO:K04377]
121308007  [KO:K16198]
121308229  e2f2; transcription factor E2F2 [KO:K09389]
121308348  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
121308524  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
121308632  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
121308896  espl1; separin [KO:K02365] [EC:3.4.22.49]
121308988  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
121309065  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
121309160  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
121309318  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
121309384  [KO:K03456]
121309512  [KO:K12456]
121309546  [KO:K02216] [EC:2.7.11.1]
121309579  [KO:K04402]
121309712  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
121310128  cdca5; sororin isoform X1 [KO:K17390]
121310839  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
121312640  [KO:K02091] [EC:2.7.11.22]
121312711  [KO:K04682]
121312791  [KO:K03347]
121312996  [KO:K05866] [EC:3.1.3.48]
121313189  dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
121313217  [KO:K06626]
121313242  [KO:K16197]
121313278  [KO:K06670]
121313292  [KO:K26116]
121313355  [KO:K06620]
121313478  mcm3l; MCM3 minichromosome maintenance deficient 3 (S. cerevisiae), like isoform X1 [KO:K02541] [EC:5.6.2.3]
121313514  [KO:K11268] [EC:2.3.1.-]
121313548  [KO:K02091] [EC:2.7.11.22]
121313658  [KO:K11580]
121313800  [KO:K02202] [EC:2.7.11.22 2.7.11.23]
121313840  mcm6l; MCM6 minichromosome maintenance deficient 6, like [KO:K02542] [EC:5.6.2.3]
121314169  [KO:K04682]
121314253  [KO:K03347]
121314339  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
121314411  mcm4; DNA replication licensing factor MCM4 isoform X1 [KO:K02212] [EC:5.6.2.3]
121314412  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
121314450  esco1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
121314608  [KO:K04377]
121314809  [KO:K06620]
121314883  [KO:K26116]
121314900  [KO:K06670]
121314939  [KO:K16197]
121314970  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
121315006  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121315026  [KO:K02091] [EC:2.7.11.22]
121315139  [KO:K11580]
121315401  [KO:K16197]
121315468  [KO:K06067] [EC:3.5.1.98]
121315690  [KO:K11584]
121315739  [KO:K04402]
121315746  [KO:K04402]
121315754  [KO:K04402]
121315761  [KO:K04402]
121315959  [KO:K11584]
121315977  [KO:K13376]
121316016  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
121316261  [KO:K08866] [EC:2.7.12.1]
121316550  fbxo5; F-box only protein 5 [KO:K10292]
121316582  [KO:K04382] [EC:3.1.3.16]
121316757  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
121316772  [KO:K11584]
121316809  [KO:K26093]
121317043  [KO:K04402]
121317063  [KO:K05868]
121317073  [KO:K05868]
121317086  [KO:K11584]
121317109  [KO:K13376]
121317116  [KO:K04402]
121317167  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
121317388  [KO:K08866] [EC:2.7.12.1]
121317484  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
121317537  ywhaqa; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide a [KO:K16197]
121317577  [KO:K06067] [EC:3.5.1.98]
121317604  orc3; origin recognition complex subunit 3 [KO:K02605]
121317833  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
121317857  [KO:K04501]
121317959  orc5; origin recognition complex subunit 5 [KO:K02607]
121317976  [KO:K06643] [EC:2.3.2.27]
121318077  [KO:K10151]
121318314  [KO:K03875]
121318354  [KO:K06672]
121318529  smc1b; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
121318537  ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
121318612  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
121318617  [KO:K06624]
121318681  [KO:K10779]
121318692  [KO:K21771]
121318698  [KO:K11405] [EC:3.5.1.98]
121318907  [KO:K06671]
121319268  [KO:K17454]
121319475  ywhaba; 14-3-3 protein beta/alpha-A isoform X1 [KO:K16197]
121319555  [KO:K06624]
121319808  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
121320013  [KO:K10151]
121320080  [KO:K06643] [EC:2.3.2.27]
121320191  rad21l1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
121320509  si:ch211-269e2.1; cohesin subunit SA-2 isoform X1 [KO:K06671]
121320698  [KO:K03353]
121320753  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121320882  [KO:K04683]
121321149  [KO:K03357]
121321153  [KO:K06618]
121321154  [KO:K06618]
121321751  [KO:K25163]
121321838  [KO:K25229]
121321859  [KO:K06669]
121321871  [KO:K02087] [EC:2.7.11.22 2.7.11.23]
121321904  [KO:K02180]
121321977  [KO:K02206] [EC:2.7.11.22]
121322312  [KO:K02542] [EC:5.6.2.3]
121322626  [KO:K02542] [EC:5.6.2.3]
121322670  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
121322825  [KO:K06671]
121323176  orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
121323520  orc4; origin recognition complex subunit 4 [KO:K02606]
121323613  [KO:K06640] [EC:2.7.11.1]
121323625  [KO:K09392]
121323749  [KO:K06627]
121323874  [KO:K11542]
121323933  [KO:K05867] [EC:3.1.3.48]
121323992  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
121324264  [KO:K11584]
121324310  [KO:K03094]
121324408  [KO:K04382] [EC:3.1.3.16]
121324567  cdc6; cell division control protein 6 homolog [KO:K02213]
121324587  [KO:K03350]
121324682  [KO:K11584]
121324708  [KO:K06629]
121324804  [KO:K13377]
121324811  [KO:K06635]
121325141  [KO:K04682]
121325210  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
121325214  [KO:K16332]
121325478  waplb; wings apart-like protein homolog isoform X1 [KO:K25163]
121325496  orc6; origin recognition complex subunit 6 [KO:K02608]
121325778  [KO:K06669]
121325792  [KO:K02087] [EC:2.7.11.22 2.7.11.23]
121326179  [KO:K02180]
121326257  [KO:K25229]
121326375  [KO:K04402]
121326434  [KO:K06622]
121326592  [KO:K06640] [EC:2.7.11.1]
121326736  [KO:K06671]
121326747  [KO:K03364]
121326932  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121326955  [KO:K05868]
121327069  [KO:K02214] [EC:2.7.11.1]
121327212  [KO:K21771]
121327247  [KO:K03363]
121327351  [KO:K09392]
121327778  [KO:K03083] [EC:2.7.11.26]
121327873  [KO:K04683]
121327963  [KO:K03353]
121328376  [KO:K13728]
121328397  [KO:K13728]
121329027  ccna2; cyclin-A2 [KO:K06627]
121329160  [KO:K10500]
121329214  [KO:K10500]
121329248  [KO:K10500]
121329330  [KO:K11267]
121329398  [KO:K10500]
121329409  [KO:K02540] [EC:5.6.2.3]
121329501  [KO:K06637] [EC:2.7.11.1]
121329871  [KO:K11584]
121329880  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
121329937  [KO:K06632] [EC:2.7.11.1]
121329999  [KO:K04503]
121330040  [KO:K11584]
121330333  [KO:K09993]
121330420  [KO:K11542]
121330472  [KO:K06631] [EC:2.7.11.21]
121330500  [KO:K06622]
121330761  orc1; origin recognition complex subunit 1 [KO:K02603]
121330907  [KO:K04402]
121330913  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121331043  [KO:K03364]
121331048  [KO:K04498] [EC:2.3.1.48]
121331115  [KO:K02214] [EC:2.7.11.1]
121331183  [KO:K03363]
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
pspa03030  DNA replication
pspa04010  MAPK signaling pathway
pspa04120  Ubiquitin mediated proteolysis
pspa04210  Apoptosis
KO pathway
ko04110   

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