KEGG   PATHWAY: epz04110
Entry
epz04110                    Pathway                                
Name
Cell cycle - Equus przewalskii (Przewalski's horse)
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
epz04110  Cell cycle
epz04110

Other DBs
GO: 0000278
Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103539994  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
103540286  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
103540562  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
103540579  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
103540763  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
103541038  ATR; serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
103541395  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
103541493  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
103541516  E2F1; transcription factor E2F1 [KO:K17454]
103541996  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
103542099  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
103542288  E2F4; transcription factor E2F4 [KO:K04682]
103542876  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103543045  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103543116  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
103543154  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
103543239  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
103543523  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103543573  [KO:K06621]
103543581  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103543777  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
103543869  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
103543986  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103546103  CCNH; cyclin-H isoform X1 [KO:K06634]
103546368  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
103546526  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103546883  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
103546922  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
103547424  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103547532  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
103547771  ORC3; origin recognition complex subunit 3 isoform X6 [KO:K02605]
103547898  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
103548140  MAD2L1BP; MAD2L1-binding protein isoform X1 [KO:K26093]
103548163  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103548488  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
103548562  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103548927  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
103549196  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
103549307  YWHAQ; 14-3-3 protein theta [KO:K16197]
103549334  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
103549440  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
103549637  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
103549644  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
103549651  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
103549781  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
103549861  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
103549989  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
103550060  CDC14A; dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103550176  CDC6; cell division control protein 6 homolog [KO:K02213]
103550408  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
103550418  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
103550537  SFN; 14-3-3 protein sigma [KO:K06644]
103550643  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
103550745  PCNA; proliferating cell nuclear antigen [KO:K04802]
103550832  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
103551012  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
103551096  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
103551213  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
103551301  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
103551352  CDC25C; M-phase inducer phosphatase 3 isoform X3 [KO:K05867] [EC:3.1.3.48]
103551353  CDC23; cell division cycle protein 23 homolog [KO:K03355]
103551624  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
103551751  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
103552097  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103552106  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103552187  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X2 [KO:K13728]
103552437  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103552647  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
103552733  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103552930  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
103552995  PTTG1; securin isoform X1 [KO:K06635]
103553025  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
103553594  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
103553644  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103553705  CUL1; cullin-1 [KO:K03347]
103553722  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
103554111  CHEK2; serine/threonine-protein kinase Chk2 isoform X6 [KO:K06641] [EC:2.7.11.1]
103554315  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103555225  YWHAZ; 14-3-3 protein zeta/delta isoform X2 [KO:K16197]
103555284  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
103555305  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
103555328  ORC5; origin recognition complex subunit 5 isoform X2 [KO:K02607]
103555506  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103555607  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103556116  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103556279  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
103556307  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
103556448  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
103557005  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
103557020  TFDP2; transcription factor Dp-2 isoform X19 [KO:K09392]
103557124  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
103557218  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103557411  CDC20; cell division cycle protein 20 homolog [KO:K03363]
103557703  TP53; cellular tumor antigen p53 [KO:K04451]
103558026  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
103558340  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103558577  ORC1; origin recognition complex subunit 1 [KO:K02603]
103559135  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
103559144  CDCA5; sororin isoform X7 [KO:K17390]
103559244  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103559350  SGO1; shugoshin 1 [KO:K11580]
103559419  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
103559559  CCNA2; cyclin-A2 [KO:K06627]
103559699  MTBP; mdm2-binding protein isoform X4 [KO:K26116]
103559812  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
103560212  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
103560745  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
103560902  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
103560975  YWHAG; 14-3-3 protein gamma [KO:K16198]
103561090  ATM; serine-protein kinase ATM isoform X3 [KO:K04728] [EC:2.7.11.1]
103561315  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
103561341  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103561450  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
103561630  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
103561774  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
103562359  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
103562411  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
103562543  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
103562657  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
103562709  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
103562771  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
103563223  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
103563383  CCNA1; cyclin-A1 [KO:K06627]
103563494  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
103563536  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
103563587  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
103563872  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
103564231  KNL1; outer kinetochore KNL1 complex subunit KNL1 isoform X1 [KO:K11542]
103564275  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
103564512  CDC14B; dual specificity protein phosphatase CDC14B isoform X14 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103564535  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103564623  CDC45; cell division control protein 45 homolog [KO:K06628]
103564670  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
103564711  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
103564848  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
103565579  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103565650  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
103565947  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
103566068  TICRR; treslin [KO:K26117]
103566139  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
103566340  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
103566452  ATRX; transcriptional regulator ATRX [KO:K10779]
103566700  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
103566925  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
103567067  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
103567186  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103567402  YWHAH; 14-3-3 protein eta [KO:K16198]
103567518  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
103567628  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
103567717  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103567860  MYC; myc proto-oncogene protein [KO:K04377]
103567910  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
103567979  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
139074407  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
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
epz03030  DNA replication
epz04010  MAPK signaling pathway
epz04120  Ubiquitin mediated proteolysis
epz04210  Apoptosis
KO pathway
ko04110   

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