KEGG   PATHWAY: gacu04110
Entry
gacu04110                   Pathway                                
Name
Cell cycle - Gymnodraco acuticeps
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
gacu04110  Cell cycle
gacu04110

Other DBs
GO: 0000278
Organism
Gymnodraco acuticeps [GN:gacu]
Gene
117532535  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
117532621  [KO:K03364]
117532640  [KO:K04503]
117532799  zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
117532846  e2f1; transcription factor E2F1 [KO:K17454]
117533257  [KO:K04682]
117533367  [KO:K06630]
117533379  [KO:K06067] [EC:3.5.1.98]
117533657  [KO:K21770]
117533777  [KO:K13377]
117534213  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
117534230  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
117534559  ep300b; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117534598  ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
117534628  [KO:K04377]
117534788  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117534863  [KO:K11542]
117534910  anapc15; anaphase-promoting complex subunit 15 [KO:K25228]
117534919  [KO:K04501]
117535020  [KO:K04382] [EC:3.1.3.16]
117535110  ccna2; cyclin-A2 [KO:K06627]
117535131  ccna1; cyclin-A1 [KO:K06627]
117535208  [KO:K06626]
117535558  chek1; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
117535635  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
117535702  cdc27; LOW QUALITY PROTEIN: cell division cycle protein 27 homolog [KO:K03350]
117535811  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117536036  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
117536172  ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
117536236  ep300a; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
117536667  [KO:K06626]
117536754  cdc23; cell division cycle protein 23 homolog [KO:K03355]
117536909  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117537477  [KO:K06670]
117537895  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
117538219  [KO:K06672]
117538269  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117538439  rb1; retinoblastoma-associated protein [KO:K06618]
117538441  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
117538463  stag2a; cohesin subunit SA-2a isoform X1 [KO:K06671]
117538482  [KO:K10779]
117538911  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117539163  [KO:K03347]
117539282  orc4; origin recognition complex subunit 4 [KO:K02606]
117539398  smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
117539794  [KO:K06620]
117539857  anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
117539925  rbl1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
117540167  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117540209  skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
117540350  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
117540403  ywhag2; 14-3-3 protein gamma-2 [KO:K16198]
117540535  [KO:K11584]
117540536  pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
117540757  [KO:K16197]
117540958  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117541063  [KO:K06671]
117541070  [KO:K11479] [EC:2.7.11.1]
117541075  [KO:K11479] [EC:2.7.11.1]
117541098  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
117541105  [KO:K03364]
117541451  [KO:K06620]
117541518  e2f5; transcription factor E2F5 [KO:K04682]
117541825  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
117542259  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
117542291  orc1; LOW QUALITY PROTEIN: origin recognition complex subunit 1 [KO:K02603]
117542588  [KO:K06670]
117542817  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
117542821  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
117542826  e2f4; transcription factor E2F4 [KO:K04682]
117542904  skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
117542925  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
117542926  [KO:K04402]
117543026  [KO:K06630]
117543377  pds5a; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
117543479  pttg1; securin [KO:K06635]
117543536  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117543627  prkdc; LOW QUALITY PROTEIN: DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
117543711  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
117543803  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
117544006  anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
117544488  si:ch211-269e2.1; LOW QUALITY PROTEIN: cohesin subunit SA-2 [KO:K06671]
117544524  cdc16; cell division cycle protein 16 homolog [KO:K03353]
117544580  [KO:K04683]
117544662  myca; transcriptional regulator Myc-A [KO:K04377]
117544997  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
117545156  dbf4b; uncharacterized protein dbf4b [KO:K06629]
117545436  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
117545443  fzr1b; fizzy-related protein homolog [KO:K03364]
117545588  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
117546168  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
117546339  ccnb3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
117546388  [KO:K11405] [EC:3.5.1.98]
117547265  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
117547802  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
117548406  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
117548459  ccndx; cyclin Dx [KO:K10151]
117548532  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117549097  cdc14ab; dual specificity protein phosphatase CDC14AB [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117549139  [KO:K04681]
117549346  smad3a; mothers against decapentaplegic homolog 3a isoform X1 [KO:K23605]
117549421  cdkn1ca; cyclin-dependent kinase inhibitor 1Ca [KO:K09993]
117549893  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
117549945  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117549969  [KO:K16197]
117549992  [KO:K06067] [EC:3.5.1.98]
117550134  orc3; origin recognition complex subunit 3 [KO:K02605]
117550376  ppp2r5b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
117550713  stag2b; cohesin subunit SA-2 [KO:K06671]
117550831  wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
117550887  [KO:K04402]
117551026  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
117551118  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
117551158  espl1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
117551473  [KO:K06622]
117551545  [KO:K16197]
117551661  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
117551767  ccnp; cyclin N-terminal domain-containing protein 2 isoform X1 [KO:K21770]
117552197  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117552767  tp53; cellular tumor antigen p53 [KO:K04451]
117553143  mad2l1bp; MAD2L1-binding protein isoform X1 [KO:K26093]
117553731  mtbp; mdm2-binding protein isoform X1 [KO:K26116]
117553797  ttk; dual specificity protein kinase Ttk [KO:K08866] [EC:2.7.12.1]
117553944  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
117553977  dbf4; protein DBF4 homolog A [KO:K06629]
117554271  ppp2r5cb; LOW QUALITY PROTEIN: protein phosphatase 2, regulatory subunit B', gamma b [KO:K11584]
117554354  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
117554769  [KO:K04500]
117554948  rad21l1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
117554972  wee1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
117555246  cdc6; LOW QUALITY PROTEIN: cell division control protein 6 homolog [KO:K02213]
117555322  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117555339  mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
117555346  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
117555508  tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
117555603  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
117555970  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
117556011  [KO:K04382] [EC:3.1.3.16]
117556355  ywhaba; 14-3-3 protein beta/alpha-A [KO:K16197]
117556388  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
117556404  e2f2; transcription factor E2F2 [KO:K09389]
117556641  orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
117556664  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
117557203  [KO:K04682]
117557281  ywhag1; 14-3-3 protein gamma-1 [KO:K16198]
117557335  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
117557475  ticrr; treslin isoform X1 [KO:K26117]
117557577  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
117557629  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
117557835  [KO:K21770]
117557839  [KO:K21770]
117558263  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
117558302  [KO:K06624]
117558435  cdc20; cell division cycle protein 20 homolog [KO:K03363]
117558472  mcm4; LOW QUALITY PROTEIN: DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
117558546  ndc80; kinetochore protein NDC80 homolog [KO:K11547]
117558616  cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
117558632  nipbla; nipped-B-like protein A isoform X1 [KO:K06672]
117558642  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
117558648  [KO:K04501]
117558763  [KO:K06671]
117558768  atr; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
117558798  [KO:K05868]
117558809  [KO:K05868]
117558914  cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
117558996  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
117559178  [KO:K10151]
117559188  orc5; origin recognition complex subunit 5 [KO:K02607]
117559400  [KO:K09993]
117559812  cdc45; cell division control protein 45 homolog [KO:K06628]
117559877  anapc4; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 4 [KO:K03351]
117560724  fbxo5; F-box only protein 5 [KO:K10292]
117560796  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
117560804  wapla; wings apart-like protein homolog isoform X1 [KO:K25163]
117561248  [KO:K03363]
117561313  pcna; proliferating cell nuclear antigen [KO:K04802]
117561595  crebbpa; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
117561675  smc3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
117562327  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
117562423  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
117562465  ccnh; cyclin-H [KO:K06634]
117562532  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
117562828  cdk6; LOW QUALITY PROTEIN: cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117562966  sgo1; shugoshin 1 isoform X1 [KO:K11580]
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
gacu03030  DNA replication
gacu04010  MAPK signaling pathway
gacu04120  Ubiquitin mediated proteolysis
gacu04210  Apoptosis
KO pathway
ko04110   

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