KEGG   PATHWAY: pcoq04110
Entry
pcoq04110                   Pathway                                
Name
Cell cycle - Propithecus coquereli (Coquerel's sifaka)
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
pcoq04110  Cell cycle
pcoq04110

Other DBs
GO: 0000278
Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105827423  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
105822622  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105807480  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
105816738  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105820132  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105813707  RB1; retinoblastoma-associated protein [KO:K06618]
105822014  RBL1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
105817052  RBL2; retinoblastoma-like protein 2 [KO:K16332]
105806618  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
105808587  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105811004  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105804948  E2F1; transcription factor E2F1 [KO:K17454]
105815699  E2F2; transcription factor E2F2 [KO:K09389]
105805737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105823359  E2F4; transcription factor E2F4 [KO:K04682]
105809737  E2F5; transcription factor E2F5 [KO:K04682]
105825134  TFDP1; transcription factor Dp-1 [KO:K04683]
105812879  TFDP2; transcription factor Dp-2 [KO:K09392]
105806400  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
105820566  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
105826908  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105819930  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
105808878  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
105821424  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105816381  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
105811323  MYC; myc proto-oncogene protein [KO:K04377]
105824950  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
105827003  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
105826999  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105806281  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
105807849  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
105819524  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105827430  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
105812249  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105812544  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105809789  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
105817322  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105826482  LOW QUALITY PROTEIN: S-phase kinase-associated protein 1-like [KO:K03094]
105816013  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
105824617  CUL1; cullin-1 [KO:K03347]
105805282  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105814809  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
105815267  CCNA2; cyclin-A2 [KO:K06627]
105810131  CCNA1; cyclin-A1 [KO:K06627]
105824247  CDC6; cell division control protein 6 homolog [KO:K02213]
105821047  CDT1; DNA replication factor Cdt1 [KO:K10727]
105806368  ORC1; origin recognition complex subunit 1 [KO:K02603]
105818997  ORC2; origin recognition complex subunit 2 [KO:K02604]
105805343  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
105822439  ORC4; origin recognition complex subunit 4 [KO:K02606]
105815173  ORC5; origin recognition complex subunit 5 [KO:K02607]
105818087  ORC6; origin recognition complex subunit 6 [KO:K02608]
105825328  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
105813800  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
105824088  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
105810687  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
105815378  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
105805982  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
105818839  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
105809826  TICRR; treslin [KO:K26117]
105812159  MTBP; mdm2-binding protein [KO:K26116]
105823762  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
105824130  DBF4B; protein DBF4 homolog B [KO:K06629]
105809658  DBF4; protein DBF4 homolog A [KO:K06629]
105821036  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
105826606  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
105821367  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
105806205  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
105812033  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
105821252  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
105806742  YWHAQ; 14-3-3 protein theta [KO:K16197]
105809776  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
105817351  YWHAE; 14-3-3 protein epsilon [KO:K06630]
105823286  YWHAH; 14-3-3 protein eta [KO:K16198]
105807025  YWHAG; 14-3-3 protein gamma [KO:K16198]
105810929  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
105818242  WEE1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
105814689  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
105813142  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
105826517  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
105820300  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
105818715  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
105819065  CDC27; cell division cycle protein 27 homolog [KO:K03350]
105826242  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
105825618  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
105824403  CDC16; cell division cycle protein 16 homolog [KO:K03353]
105823228  LOW QUALITY PROTEIN: cell division cycle protein 16 homolog [KO:K03353]
105825612  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
105811993  CDC23; cell division cycle protein 23 homolog [KO:K03355]
105808981  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
105820024  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
105807742  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
105826452  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
105811495  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
105825483  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
105814100  CDC20; cell division cycle protein 20 homolog [KO:K03363]
105823867  securin-like [KO:K06635]
105810772  PTTG1; securin [KO:K06635]
105817396  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
105822748  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
105823440  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
105826017  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
105813814  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
105825548  STAG1; cohesin subunit SA-1 [KO:K06671]
105826805  STAG2; cohesin subunit SA-2 [KO:K06671]
105826151  ATRX; transcriptional regulator ATRX [KO:K10779]
105823967  DDX11; LOW QUALITY PROTEIN: probable ATP-dependent RNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
105814458  NIPBL; LOW QUALITY PROTEIN: nipped-B-like protein [KO:K06672]
105818149  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
105809885  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
105825223  ESCO2; LOW QUALITY PROTEIN: N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
105816609  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
105808478  PDS5B; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
105810474  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
105815975  WAPAL; wings apart-like protein homolog [KO:K25163]
105827262  CDCA5; sororin [KO:K17390]
105819384  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
105825868  SGOL1; shugoshin-like 1 isoform X1 [KO:K11580]
105813802  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105816012  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105822194  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
105809563  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105819900  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
105827459  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105812602  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105807462  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
105805455  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
105816595  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
105814300  CASC5; LOW QUALITY PROTEIN: protein CASC5 [KO:K11542]
105811769  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
105806053  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
105806410  mitotic spindle assembly checkpoint protein MAD2A-like [KO:K02537]
105811207  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
105824963  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
105814453  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
105808699  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
105808351  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
105825816  pachytene checkpoint protein 2 homolog [KO:K22399]
105823059  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
105807471  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
105811970  FZR1; fizzy-related protein homolog [KO:K03364]
105812363  FBXO5; F-box only protein 5 [KO:K10292]
105818765  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105806837  CDC14B; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105813122  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
105805288  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105824093  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
105812887  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
105822182  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
105812777  E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105819395  TP53; cellular tumor antigen p53 [KO:K04451]
105811966  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105817781  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105817934  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105806199  PCNA; proliferating cell nuclear antigen [KO:K04802]
105811694  SFN; 14-3-3 protein sigma [KO:K06644]
105821450  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
105810166  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
105811317  CDC25A; M-phase inducer phosphatase 1 isoform X1 [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.
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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
pcoq03030  DNA replication
pcoq04010  MAPK signaling pathway
pcoq04120  Ubiquitin mediated proteolysis
pcoq04210  Apoptosis
KO pathway
ko04110   
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