KEGG   PATHWAY: cpla04110
Entry
cpla04110                   Pathway                                
Name
Cell cycle - Chiloscyllium plagiosum (whitespotted bambooshark)
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
cpla04110  Cell cycle
cpla04110

Other DBs
GO: 0000278
Organism
Chiloscyllium plagiosum (whitespotted bambooshark) [GN:cpla]
Gene
122539324  [KO:K06627]
122539461  [KO:K04382] [EC:3.1.3.16]
122539462  [KO:K03094]
122539821  cdc6; cell division control protein 6 homolog [KO:K02213]
122539902  [KO:K02091] [EC:2.7.11.22]
122540030  cdc27; cell division cycle protein 27 homolog [KO:K03350]
122540071  anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
122540260  zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
122540324  mad2l2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
122540646  ppp2r1ba; protein phosphatase 2, regulatory subunit A, beta a isoform X1 [KO:K03456]
122540681  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
122540735  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
122540896  smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605]
122540934  ticrr; treslin isoform X1 [KO:K26117]
122541009  ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
122541355  ywhaqa; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide a [KO:K16197]
122541916  anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
122541951  [KO:K25163]
122541966  [KO:K04503]
122542028  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
122542299  [KO:K04498] [EC:2.3.1.48]
122542300  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
122542358  [KO:K06636]
122542842  [KO:K13377]
122543049  pcna; proliferating cell nuclear antigen [KO:K04802]
122543277  cdk4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
122543338  cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122543388  tp53; cellular tumor antigen p53 [KO:K04451]
122543863  cdca5; sororin isoform X1 [KO:K17390]
122544248  [KO:K03456]
122544362  mcm7; LOW QUALITY PROTEIN: DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
122544408  [KO:K06671]
122544738  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
122545806  [KO:K06067] [EC:3.5.1.98]
122546347  esco2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
122546714  [KO:K06625]
122547196  [KO:K06632] [EC:2.7.11.1]
122547841  [KO:K11584]
122548044  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
122548305  [KO:K16198]
122548352  orc3; origin recognition complex subunit 3 [KO:K02605]
122548385  ttk; dual specificity protein kinase Ttk [KO:K08866] [EC:2.7.12.1]
122548466  [KO:K02178] [EC:2.7.11.1]
122548555  [KO:K26093]
122548569  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
122548983  ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
122549046  [KO:K11268] [EC:2.3.1.-]
122549078  prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
122549079  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
122549153  [KO:K16197]
122549176  [KO:K04377]
122549231  [KO:K26116]
122549342  rad21b; RAD21 cohesin complex component b [KO:K06670]
122549749  cdk6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
122549915  [KO:K03347]
122549944  [KO:K11580]
122549995  [KO:K06629]
122550478  cdc16; cell division cycle protein 16 homolog [KO:K03353]
122550707  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
122550904  si:ch211-269e2.1; cohesin subunit SA-2 isoform X1 [KO:K06671]
122550967  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
122551064  [KO:K11267]
122551065  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
122551160  ccna1; cyclin-A1 isoform X1 [KO:K06627]
122551295  [KO:K02206] [EC:2.7.11.22]
122551379  orc2; origin recognition complex subunit 2 [KO:K02604]
122551696  [KO:K02542] [EC:5.6.2.3]
122551738  orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
122552238  [KO:K06623]
122552546  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
122552681  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
122552812  tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122552842  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
122553104  mad2l1; mitotic spindle assembly checkpoint protein MAD2A isoform X1 [KO:K02537]
122553197  fbxo5; F-box only protein 5 isoform X1 [KO:K10292]
122553452  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon [KO:K11584]
122553513  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
122553816  bub1bb; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
122553838  knl1; kinetochore scaffold 1 isoform X1 [KO:K11542]
122554170  cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
122554231  cdc20; cell division cycle protein 20 homolog [KO:K03363]
122554276  anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
122554322  [KO:K03364]
122554332  orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
122554350  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
122554524  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122554776  [KO:K04402]
122554940  [KO:K03363]
122554942  rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
122555004  anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
122555232  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122555463  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
122555796  [KO:K06671]
122556218  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
122556221  [KO:K09392]
122556264  [KO:K06672]
122556303  skp2; S-phase kinase-associated protein 2 [KO:K03875]
122556585  skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
122556586  [KO:K04382] [EC:3.1.3.16]
122556741  pttg1; securin [KO:K06635]
122556841  cdc23; cell division cycle protein 23 homolog [KO:K03355]
122556870  [KO:K05867] [EC:3.1.3.48]
122557166  hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
122557227  ccnb3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
122557312  stag2b; cohesin subunit SA-2 isoform X1 [KO:K06671]
122557356  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
122557396  [KO:K04683]
122557612  ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
122557943  cdkn1cb; cyclin-dependent kinase inhibitor 1C [KO:K09993]
122558191  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
122558254  cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
122558314  cdt1; DNA replication factor Cdt1 [KO:K10727]
122558371  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
122558387  orc6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
122558574  e2f4; transcription factor E2F4 [KO:K04682]
122558735  rbl2; retinoblastoma-like protein 2 [KO:K16332]
122558812  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
122559295  ccnh; cyclin-H isoform X1 [KO:K06634]
122559328  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
122559458  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
122559463  [KO:K06632] [EC:2.7.11.1]
122559576  [KO:K06636]
122559649  [KO:K06625]
122559883  [KO:K06670]
122559888  rbl1; retinoblastoma-like protein 1 [KO:K04681]
122560268  [KO:K17454]
122560317  [KO:K16197]
122560629  [KO:K04498] [EC:2.3.1.48]
122560724  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
122560761  mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
122561030  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
122561164  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
122561359  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
122561627  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122561684  ccnd2a; G1/S-specific cyclin-D2a isoform X1 [KO:K10151]
122561750  orc5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
122561793  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
122562183  anapc11; anaphase-promoting complex subunit 11 isoform X1 [KO:K03358]
122562547  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
122562663  anapc7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
122562674  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
122562813  cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
122563112  ccnd3; G1/S-specific cyclin-D3 [KO:K10151]
122563388  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
122563452  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
122563554  [KO:K16197]
122563614  e2f2; transcription factor E2F2 isoform X1 [KO:K09389]
122563877  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
122564154  [KO:K16198]
122564172  [KO:K11479] [EC:2.7.11.1]
122564188  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122564376  [KO:K06620]
122564449  trip13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
122564712  anapc2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
122564733  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
122564931  smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
122564979  abl1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
122565165  ndc80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
122565304  fzr1a; fizzy/cell division cycle 20 related 1a isoform X1 [KO:K03364]
122565379  [KO:K05868]
122565427  [KO:K04402]
122565464  mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
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
  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
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
Oncogene 24:2796-809 (2005)
DOI:10.1038/sj.onc.1208619
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
cpla03030  DNA replication
cpla04010  MAPK signaling pathway
cpla04120  Ubiquitin mediated proteolysis
cpla04210  Apoptosis
KO pathway
ko04110   

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