KEGG   PATHWAY: gja04110
Entry
gja04110                    Pathway                                
Name
Cell cycle - Gekko japonicus (Schlegel's Japanese gecko)
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
gja04110  Cell cycle
gja04110

Other DBs
GO: 0000278
Organism
Gekko japonicus (Schlegel's Japanese gecko) [GN:gja]
Gene
107121511  CCND1; cyclin D1 [KO:K04503]
107110411  CCND2; cyclin D2 [KO:K10151]
107119188  CCND3; cyclin D3 [KO:K10152]
107119665  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
107108272  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
107112871  RB1; RB transcriptional corepressor 1 [KO:K06618]
107122224  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
107119664  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
107108928  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
107107742  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
107121973  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
107122240  E2F1; E2F transcription factor 1 [KO:K17454]
107109576  E2F2; E2F transcription factor 2 [KO:K09389]
107121911  E2F3; E2F transcription factor 3 [KO:K06620]
107118852  E2F4; E2F transcription factor 4 [KO:K04682]
107122380  E2F5; E2F transcription factor 5 [KO:K04682]
107110920  TFDP1; transcription factor Dp-1 [KO:K04683]
107112350  TFDP2; transcription factor Dp-2 [KO:K09392]
107109342  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
107123911  TGFB1; transforming growth factor beta 1 [KO:K13375]
107110247  TGFB2; transforming growth factor beta 2 [KO:K13376]
107115203  transforming growth factor beta-2-like [KO:K13376]
107116455  TGFB3; transforming growth factor beta 3 [KO:K13377]
107118628  SMAD2; SMAD family member 2 [KO:K04500]
107105564  SMAD3; SMAD family member 3 [KO:K23605]
107110886  mothers against decapentaplegic homolog 4-like [KO:K04501]
107122009  SMAD4; SMAD family member 4 [KO:K04501]
107122472  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
107111606  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
107124310  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
107124306  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
107116289  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
107125498  cyclin-dependent kinase 4 inhibitor D-like [KO:K06623]
107122416  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
107113521  CDKN1C; cyclin dependent kinase inhibitor 1C [KO:K09993]
107117358  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
107111179  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
107109268  CCNE2; cyclin E2 [KO:K06626]
107111199  CCNE1; cyclin E1 [KO:K06626]
107105847  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
107125984  SKP1; S-phase kinase associated protein 1 [KO:K03094]
107119625  CUL1; cullin 1 [KO:K03347]
107117140  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
107108086  SKP2; S-phase kinase associated protein 2 [KO:K03875]
107115396  CCNA2; cyclin A2 [KO:K06627]
107117465  CCNA1; cyclin A1 [KO:K06627]
107108821  CDC6; cell division cycle 6 [KO:K02213]
107115626  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
107111058  ORC1; origin recognition complex subunit 1 [KO:K02603]
107108262  ORC2; origin recognition complex subunit 2 [KO:K02604]
107121752  ORC3; origin recognition complex subunit 3 [KO:K02605]
107108800  ORC4; origin recognition complex subunit 4 [KO:K02606]
107113717  ORC5; origin recognition complex subunit 5 [KO:K02607]
107108886  ORC6; origin recognition complex subunit 6 [KO:K02608]
107122941  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
107122362  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
107109424  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
107115413  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
107114901  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
107115241  CDC45; cell division cycle 45 [KO:K06628]
107117179  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
107111103  MTBP; MDM2 binding protein [KO:K26116]
107117982  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
107121252  DBF4; DBF4 zinc finger [KO:K06629]
107114753  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
107115487  CCNB1; cyclin B1 [KO:K05868]
107117975  CCNB2; cyclin B2 [KO:K21770]
107108496  CCNB3; cyclin B3 [KO:K21771]
107108364  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
107107149  M-phase inducer phosphatase 1-B-like [KO:K05867] [EC:3.1.3.48]
107112822  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
107116159  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
107124741  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
107119435  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
107107681  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
107115108  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
107126199  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
107109690  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
107121728  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
107105462  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
107107224  CCNH; cyclin H [KO:K06634]
107115490  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
107114598  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
107115160  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
107118451  CDC27; cell division cycle 27 [KO:K03350]
107115126  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
107115889  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
107125853  CDC16; cell division cycle 16 [KO:K03353]
107115883  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
107111549  CDC23; cell division cycle 23 [KO:K03355]
107120273  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
107118133  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
107120426  CDC26; cell division cycle 26 [KO:K03359]
107106500  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
107115795  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
107107388  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
107106429  CDC20; cell division cycle 20 [KO:K03363]
107114410  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
107118969  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
107105467  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
107117369  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
107121823  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
107120188  RAD21L1; RAD21 cohesin complex component like 1 [KO:K06670]
107110229  cohesin subunit SA-2-like [KO:K06671]
107123605  STAG1; stromal antigen 1 [KO:K06671]
107123685  STAG2; stromal antigen 2 [KO:K06671]
107123232  ATRX; ATRX, chromatin remodeler [KO:K10779]
107108295  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
107108087  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
107114095  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
107108500  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
107113794  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
107120576  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
107116459  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
107118220  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
107120663  WAPL; WAPL cohesin release factor [KO:K25163]
107110114  CDCA5; cell division cycle associated 5 [KO:K17390]
107111923  aurora kinase C-like [KO:K11479] [EC:2.7.11.1]
107120722  aurora kinase B-A-like [KO:K11479] [EC:2.7.11.1]
107123662  SGO1; shugoshin 1 [KO:K11580]
107125982  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
107110575  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107124393  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
107116652  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
107123087  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
107124204  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
107110121  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
107124785  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
107112742  NDC80; NDC80, kinetochore complex component [KO:K11547]
107113923  KNL1; kinetochore scaffold 1 [KO:K11542]
107109436  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
107119572  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
107117277  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
107117730  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
107119644  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
107120702  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
107114594  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
107115923  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
107119058  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
107112882  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
107109008  FBXO5; F-box protein 5 [KO:K10292]
107107444  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
107111670  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
107109304  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
107117161  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
107122359  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
107112351  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
107113474  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
107105724  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
107121079  TP53; tumor protein p53 [KO:K04451]
107108632  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
107114354  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
107120631  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
107118755  PCNA; proliferating cell nuclear antigen [KO:K04802]
107108892  SFN; stratifin [KO:K06644]
107117803  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
107123921  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
107124887  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
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
gja03030  DNA replication
gja04010  MAPK signaling pathway
gja04120  Ubiquitin mediated proteolysis
gja04210  Apoptosis
KO pathway
ko04110   
LinkDB

DBGET integrated database retrieval system