KEGG   PATHWAY: psex04110
Entry
psex04110                   Pathway                                
Name
Cell cycle - Polypterus senegalus (gray bichir)
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
psex04110  Cell cycle
psex04110

Other DBs
GO: 0000278
Organism
Polypterus senegalus (gray bichir) [GN:psex]
Gene
120514402  orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
120514438  [KO:K03364]
120514495  rbl1; retinoblastoma-like protein 1 [KO:K04681]
120514618  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
120514988  [KO:K04402]
120515087  ywhaba; 14-3-3 protein beta/alpha-A [KO:K16197]
120515365  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
120515507  [KO:K26116]
120515877  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120516274  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
120516276  [KO:K06670]
120516589  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
120517030  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
120517306  [KO:K06067] [EC:3.5.1.98]
120517445  cdc27; cell division cycle protein 27 homolog [KO:K03350]
120517832  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
120517873  cdc6; cell division control protein 6 homolog [KO:K02213]
120518044  e2f2; transcription factor E2F2 [KO:K09389]
120518279  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120518451  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
120519107  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X1 [KO:K11584]
120519225  [KO:K06623]
120519300  gadd45bb; growth arrest and DNA-damage-inducible, beta b [KO:K04402]
120522242  [KO:K10151]
120522916  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120523299  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
120523386  tfdp1b; transcription factor Dp-1b isoform X1 [KO:K04683]
120523440  [KO:K09993]
120523454  cdc16; cell division cycle protein 16 homolog [KO:K03353]
120523940  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
120523990  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
120524008  ccna1; cyclin-A1 [KO:K06627]
120524037  rb1; retinoblastoma-associated protein [KO:K06618]
120524416  si:ch211-269e2.1; cohesin subunit SA-2 [KO:K06671]
120524842  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
120524900  espl1; separin [KO:K02365] [EC:3.4.22.49]
120525038  tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
120525101  aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
120525203  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
120525240  [KO:K06671]
120525242  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
120525557  [KO:K06067] [EC:3.5.1.98]
120525589  orc3; origin recognition complex subunit 3 [KO:K02605]
120525626  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
120525785  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
120525820  [KO:K02541] [EC:5.6.2.3]
120525945  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
120526039  ywhaqa; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide a [KO:K16197]
120526216  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
120527108  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
120527232  smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
120527290  skp2; S-phase kinase-associated protein 2 [KO:K03875]
120527294  nipblb; nipped-B-like protein B isoform X1 [KO:K06672]
120527577  ccna2; cyclin-A2 [KO:K06627]
120527585  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
120527663  pds5a; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
120527946  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
120529478  cul1b; cullin-1b [KO:K03347]
120529802  [KO:K04377]
120529863  mcm3l; MCM3 minichromosome maintenance deficient 3 (S. cerevisiae), like [KO:K02541] [EC:5.6.2.3]
120530131  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
120530210  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
120530212  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
120530826  zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
120531009  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
120531410  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
120531590  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
120531703  orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
120531715  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
120531920  orc2; origin recognition complex subunit 2 [KO:K02604]
120532213  [KO:K04402]
120532214  [KO:K04402]
120532405  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
120532555  [KO:K05868]
120532556  [KO:K05868]
120532622  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120532656  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120532865  ccnh; cyclin-H [KO:K06634]
120532948  [KO:K04402]
120533041  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120533086  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
120533408  [KO:K09392]
120533470  atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
120533716  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120533731  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
120534209  stag1a; cohesin subunit SA-1a [KO:K06671]
120535215  rbl2; retinoblastoma-like protein 2 [KO:K16332]
120535355  orc6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
120535368  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
120535403  e2f4; transcription factor E2F4 [KO:K04682]
120535427  cdt1; DNA replication factor Cdt1 [KO:K10727]
120535843  [KO:K03456]
120535889  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
120536002  abl1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
120536445  ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120536605  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
120536924  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120536925  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
120537092  hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
120537093  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
120537399  stag2b; cohesin subunit SA-2 isoform X1 [KO:K06671]
120537476  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
120537617  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
120537868  fzr1a; fizzy/cell division cycle 20 related 1a [KO:K03364]
120537961  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
120537977  cdc14ab; dual specificity protein phosphatase CDC14AB isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120538014  e2f1; transcription factor E2F1 [KO:K17454]
120538179  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
120538772  [KO:K13375]
120538836  pcna; proliferating cell nuclear antigen [KO:K04802]
120539297  waplb; wings apart-like protein homolog [KO:K25163]
120539363  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
120539446  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
120539581  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
120539608  orc5; origin recognition complex subunit 5 [KO:K02607]
120539654  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
120539697  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
120539988  chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
120540086  [KO:K03456]
120540527  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
120540576  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
120540696  [KO:K16198]
120540811  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
120540950  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
120540969  cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
120541226  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
120541663  smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605]
120541798  ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
120541877  cdc23; cell division cycle protein 23 homolog [KO:K03355]
120541878  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
120541898  [KO:K04498] [EC:2.3.1.48]
120541988  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
120542003  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120542019  [KO:K05867] [EC:3.1.3.48]
120542076  skp1; S-phase kinase-associated protein 1 [KO:K03094]
120542681  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
120542830  [KO:K04503]
120542996  cdc26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
120543042  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
120543191  [KO:K10152]
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
psex03030  DNA replication
psex04010  MAPK signaling pathway
psex04120  Ubiquitin mediated proteolysis
psex04210  Apoptosis
KO pathway
ko04110   

DBGET integrated database retrieval system