KEGG   PATHWAY: mcep04110
Entry
mcep04110                   Pathway                                
Name
Cell cycle - Mugil cephalus (flathead mullet)
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
mcep04110  Cell cycle
mcep04110

Other DBs
GO: 0000278
Organism
Mugil cephalus (flathead mullet) [GN:mcep]
Gene
124995515  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
124995915  mycA; transcriptional regulator Myc-A isoform X1 [KO:K04377]
124996351  skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
124996415  smad4a; mothers against decapentaplegic homolog 4a isoform X1 [KO:K04501]
124996509  [KO:K06672]
124996567  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
124996760  [KO:K04402]
124996911  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
124997033  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
124997146  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
124997156  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
124997363  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
124997461  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
124997635  [KO:K04498] [EC:2.3.1.48]
124997726  cdc27; cell division cycle protein 27 homolog [KO:K03350]
124997818  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
124998171  ccndx; cyclin Dx [KO:K10151]
124998308  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
124998349  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
124998495  ccnb3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
124998758  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
124998792  [KO:K06067] [EC:3.5.1.98]
124998919  ppp2r5cb; protein phosphatase 2, regulatory subunit B', gamma b isoform X1 [KO:K11584]
124998992  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
124999390  [KO:K13377]
124999463  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
124999875  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
124999996  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
125000184  [KO:K10151]
125000259  orc5; origin recognition complex subunit 5 [KO:K02607]
125000358  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
125000664  orc4; origin recognition complex subunit 4 [KO:K02606]
125003697  cdc6; cell division control protein 6 homolog [KO:K02213]
125003970  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
125004195  [KO:K04498] [EC:2.3.1.48]
125004367  mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
125004481  cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K04685]
125004565  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
125004676  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
125004766  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
125004918  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
125005256  ccnb2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
125005272  smad3a; mothers against decapentaplegic homolog 3a [KO:K23605]
125005545  [KO:K04682]
125005606  cdkn1ca; cyclin-dependent kinase inhibitor 1Ca [KO:K09993]
125005752  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
125006303  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
125006409  ywhaba; 14-3-3 protein beta/alpha-A [KO:K16197]
125006700  rbl1; retinoblastoma-like protein 1 [KO:K04681]
125006852  mycH; myelocytomatosis oncogene homolog [KO:K04377]
125006926  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
125007216  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
125007293  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
125007318  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
125007346  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
125007380  espl1; separin [KO:K02365] [EC:3.4.22.49]
125007649  aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
125007910  atrX; transcriptional regulator ATRX isoform X1 [KO:K10779]
125007955  stag2b; cohesin subunit SA-2 isoform X1 [KO:K06671]
125008041  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
125008120  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
125008205  [KO:K06671]
125008379  mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
125008468  [KO:K04382] [EC:3.1.3.16]
125008640  ccna2; cyclin-A2 [KO:K06627]
125008675  pttg1; securin [KO:K06635]
125008790  orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
125008816  [KO:K03364]
125009111  [KO:K11266]
125009154  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
125009205  cdc14ab; dual specificity protein phosphatase CDC14AB isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
125009532  cdkn2c; cyclin-dependent kinase 4 inhibitor C isoform X1 [KO:K06622]
125009799  [KO:K04402]
125009995  gadd45ab; growth arrest and DNA-damage-inducible, alpha, B [KO:K04402]
125010071  [KO:K03364]
125010152  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
125010254  [KO:K04451]
125010359  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
125010497  orc2; origin recognition complex subunit 2 [KO:K02604]
125010522  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
125010818  e2f5; transcription factor E2F5 [KO:K04682]
125011002  [KO:K04377]
125011129  fzr1b; fizzy-related protein homolog isoform X1 [KO:K03364]
125011302  cdc20; cell division cycle protein 20 homolog [KO:K03363]
125011433  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
125011465  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
125011470  gadd45aa; growth arrest and DNA-damage-inducible, alpha, A [KO:K04402]
125011657  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
125011668  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
125011945  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
125011988  ccnH; cyclin-H [KO:K06634]
125012075  nipbla; nipped-B-like protein A isoform X1 [KO:K06672]
125012113  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
125012238  [KO:K04500]
125012255  cdc45; cell division control protein 45 homolog [KO:K06628]
125012530  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
125012591  [KO:K04501]
125012628  pcnA; proliferating cell nuclear antigen [KO:K04802]
125012658  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
125012681  [KO:K16197]
125012809  [KO:K04382] [EC:3.1.3.16]
125012810  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
125012907  gadd45ga; growth arrest and DNA-damage-inducible, gamma A [KO:K04402]
125012932  [KO:K03363]
125013193  ywhag2; 14-3-3 protein gamma-B [KO:K16198]
125013214  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
125013280  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
125013340  [KO:K21770]
125013391  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
125013405  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
125013476  tgfb1a; transforming growth factor, beta 1a isoform X1 [KO:K13375]
125014314  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
125014367  [KO:K04503]
125014371  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
125014586  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
125014785  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
125014816  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
125014854  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
125014886  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
125015146  zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
125015288  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
125015299  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
125015359  smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
125015389  e2f4; transcription factor E2F4 [KO:K04682]
125015454  ticrr; treslin isoform X1 [KO:K26117]
125015463  cdkn1cb; cyclin-dependent kinase inhibitor 1C [KO:K09993]
125015769  dbf4; protein DBF4 homolog A [KO:K06629]
125015992  [KO:K04501]
125016189  ttk; LOW QUALITY PROTEIN: dual specificity protein kinase Ttk [KO:K08866] [EC:2.7.12.1]
125016476  [KO:K06670]
125016502  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
125016524  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
125016821  [KO:K16197]
125016968  [KO:K06620]
125017023  [KO:K26116]
125017054  ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
125017307  cdc16; cell division cycle protein 16 homolog [KO:K03353]
125017410  [KO:K06671]
125017415  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
125017729  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125017927  [KO:K04683]
125018334  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
125018390  cdt1; DNA replication factor Cdt1 [KO:K10727]
125018768  rad21l1; double-strand-break repair protein rad21-like protein 1 isoform X1 [KO:K06670]
125018788  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
125018891  wapla; wings apart-like protein homolog [KO:K25163]
125018900  fbxo5; F-box only protein 5 [KO:K10292]
125019113  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
125019157  [KO:K26093]
125019430  sgo1; shugoshin 1 isoform X1 [KO:K11580]
125019542  [KO:K04451]
125019568  [KO:K04451]
125019584  [KO:K04451]
125019606  e2f3; transcription factor E2F3 [KO:K06620]
125019739  [KO:K16197]
125019848  [KO:K06067] [EC:3.5.1.98]
125019878  cdca5; sororin [KO:K17390]
125020145  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
125020375  [KO:K06670]
125020803  [KO:K10779]
125020944  skp1; S-phase kinase-associated protein 1 [KO:K03094]
125020956  rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
125020971  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
125021233  e2f1; transcription factor E2F1 [KO:K17454]
125021390  [KO:K06671]
125021597  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
125021629  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
125021673  [KO:K06630]
125021709  cdc23; cell division cycle protein 23 homolog [KO:K03355]
125021744  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
125021796  ccna1; cyclin-A1 [KO:K06627]
125021994  bub3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
125022069  dbf4b; uncharacterized protein dbf4b isoform X1 [KO:K06629]
125022195  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
125022345  [KO:K25163]
125022600  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
125023289  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
125023316  [KO:K04402]
125023326  [KO:K13377]
125023344  stag1a; cohesin subunit SA-1a [KO:K06671]
125023392  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
125023491  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X1 [KO:K11584]
125023602  [KO:K16197]
125023716  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
125023804  [KO:K06067] [EC:3.5.1.98]
125023984  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
125023999  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
125024058  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
125024276  e2f2; transcription factor E2F2 [KO:K09389]
125024463  [KO:K03347]
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
mcep03030  DNA replication
mcep04010  MAPK signaling pathway
mcep04120  Ubiquitin mediated proteolysis
mcep04210  Apoptosis
KO pathway
ko04110   

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