KEGG   PATHWAY: csab04110
Entry
csab04110                   Pathway                                
Name
Cell cycle - Chlorocebus sabaeus (green monkey)
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
csab04110  Cell cycle
csab04110

Other DBs
GO: 0000278
Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103246489  CCND1; cyclin D1 [KO:K04503]
103218410  CCND2; cyclin D2 [KO:K10151]
103221504  CCND3; cyclin D3 [KO:K10152]
103238589  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103226555  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103214406  RB1; RB transcriptional corepressor 1 [KO:K06618]
103232914  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
103239742  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
103225192  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103240535  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103239354  histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
103248605  E2F1; E2F transcription factor 1 [KO:K17454]
103225395  E2F2; E2F transcription factor 2 [KO:K09389]
103222084  E2F3; E2F transcription factor 3 [KO:K06620]
103233300  E2F4; E2F transcription factor 4 [KO:K04682]
103237062  E2F5; E2F transcription factor 5 [KO:K04682]
103214851  TFDP1; transcription factor Dp-1 [KO:K04683]
103241562  TFDP2; transcription factor Dp-2 [KO:K09392]
103228213  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103234729  TGFB1; transforming growth factor beta 1 [KO:K13375]
103230082  TGFB2; transforming growth factor beta 2 [KO:K13376]
103229367  TGFB3; transforming growth factor beta 3 [KO:K13377]
103222457  SMAD2; SMAD family member 2 [KO:K04500]
103245436  SMAD3; SMAD family member 3 [KO:K23605]
103222414  SMAD4; SMAD family member 4 [KO:K04501]
103237430  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103225537  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
103219354  cyclin-dependent kinase inhibitor 2A, isoform 4 [KO:K06621]
103219356  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
103224834  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
103233902  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
103218647  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
103241276  CDKN1C; cyclin dependent kinase inhibitor 1C [KO:K09993]
103221583  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103237156  CCNE2; cyclin E2 [KO:K06626]
103235482  CCNE1; cyclin E1 [KO:K06626]
103238495  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
103244544  SKP1; S-phase kinase associated protein 1 [KO:K03094]
103227180  CUL1; cullin 1 [KO:K03347]
103223367  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
103215131  SKP2; S-phase kinase associated protein 2 [KO:K03875]
103214281  CCNA1; cyclin A1 [KO:K06627]
103236201  CCNA2; cyclin A2 [KO:K06627]
103243516  CDC6; cell division cycle 6 [KO:K02213]
103233458  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
103224814  ORC1; origin recognition complex subunit 1 [KO:K02603]
103217623  ORC2; origin recognition complex subunit 2 [KO:K02604]
103240070  ORC3; origin recognition complex subunit 3 [KO:K02605]
103217056  ORC4; origin recognition complex subunit 4 [KO:K02606]
103226688  ORC5; origin recognition complex subunit 5 [KO:K02607]
103232184  ORC6; origin recognition complex subunit 6 [KO:K02608]
103228108  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
103221368  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
103236759  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
103223231  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
103216989  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
103246753  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
103223001  CDC45; cell division cycle 45 [KO:K06628]
103231499  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
103237353  MTBP; MDM2 binding protein [KO:K26116]
103224447  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
103226602  DBF4; DBF4 zinc finger [KO:K06629]
103243316  DBF4B; DBF4 zinc finger B [KO:K06629]
103216148  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103222804  CCNB1; cyclin B1 [KO:K05868]
103245548  CCNB2; cyclin B2 [KO:K21770]
103231980  CCNB3; cyclin B3 [KO:K21771]
103247543  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
103244613  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
103237221  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
103220843  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
103245470  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
103242121  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
103223201  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
103246662  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
103229799  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
103240451  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
103227031  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
103227033  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
103224232  CCNH; cyclin H [KO:K06634]
103222774  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
103241259  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
103239578  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
103243273  CDC27; cell division cycle 27 [KO:K03350]
103246266  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
103239279  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
103214862  CDC16; cell division cycle 16 [KO:K03353]
103239524  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
103244615  CDC23; cell division cycle 23 [KO:K03355]
103236325  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
103243735  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
103218996  CDC26; cell division cycle 26 [KO:K03359]
103241635  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
103247989  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
103216030  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
103224971  CDC20; cell division cycle 20 [KO:K03363]
103244908  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
103238749  securin-like [KO:K06635]
103238391  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
103238388  separin-like [KO:K02365] [EC:3.4.22.49]
103223473  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
103232930  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
103216505  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
103237327  RAD21; RAD21 cohesin complex component [KO:K06670]
103241625  STAG1; stromal antigen 1 [KO:K06671]
103247377  STAG2; stromal antigen 2 [KO:K06671]
103232231  ATRX; ATRX, chromatin remodeler [KO:K10779]
103218547  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
103215143  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
103234216  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
103232180  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
103222667  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
103215530  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
103246196  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
103214259  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
103215878  WAPL; WAPL cohesin release factor [KO:K25163]
103231219  CDCA5; cell division cycle associated 5 [KO:K17390]
103241905  uncharacterized LOC103241905 [KO:K17390]
103242347  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
103241749  SGO1; shugoshin 1 [KO:K11580]
103244545  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
103215586  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
103235167  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
103248442  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
103232471  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
103221482  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
103230127  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
103229722  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
103229152  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
103222693  NDC80; NDC80, kinetochore complex component [KO:K11547]
103246102  KNL1; kinetochore scaffold 1 [KO:K11542]
103239980  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
103246871  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
103236183  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
103225603  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
103245845  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
103216653  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
103241243  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
103214906  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
103221450  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
103233682  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
103240744  FBXO5; F-box protein 5 [KO:K10292]
103224365  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103226087  dual specificity protein phosphatase CDC14C [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103219812  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103231770  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
103223371  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
103236758  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
103241557  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
103248401  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
103238687  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103242323  TP53; tumor protein p53 [KO:K04451]
103224652  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
103233650  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
103219731  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
103242170  proliferating cell nuclear antigen-like [KO:K04802]
103246929  PCNA; proliferating cell nuclear antigen [KO:K04802]
103225311  SFN; stratifin [KO:K06644]
103248769  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
103223122  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
103228635  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
csab03030  DNA replication
csab04010  MAPK signaling pathway
csab04120  Ubiquitin mediated proteolysis
csab04210  Apoptosis
KO pathway
ko04110   
LinkDB

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