KEGG   PATHWAY: ocu04110
Entry
ocu04110                    Pathway                                
Name
Cell cycle - Oryctolagus cuniculus (rabbit)
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
ocu04110  Cell cycle
ocu04110

Other DBs
GO: 0000278
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008645  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100008930  YWHAQ; 14-3-3 protein theta [KO:K16197]
100009036  G1/S-specific cyclin-D2 [KO:K10151]
100009037  cyclin-dependent kinase inhibitor 1B [KO:K06624]
100009038  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100009039  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100009040  cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
100009215  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100009216  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
100009252  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100009292  TP53; cellular tumor antigen p53 [KO:K04451]
100009300  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100009371  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100009434  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
100009533  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100125348  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
100134864  G1/S-specific cyclin-E1 [KO:K06626]
100134865  cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100134866  CCNA2; cyclin-A2 [KO:K06627]
100134867  G1/S-specific cyclin-E2 isoform X3 [KO:K06626]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100328701  STAG2; cohesin subunit SA-2 [KO:K06671]
100328734  YWHAH; 14-3-3 protein eta [KO:K16198]
100337867  structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
100337896  DNA replication licensing factor MCM2 isoform X1 [KO:K02540] [EC:5.6.2.3]
100338447  S-phase kinase-associated protein 2-like [KO:K03875]
100338660  origin recognition complex subunit 3 isoform X5 [KO:K02605]
100338921  anaphase-promoting complex subunit 15-like [KO:K25228]
100338989  G2/mitotic-specific cyclin-B1 [KO:K05868]
100339152  protein DBF4 homolog A isoform X1 [KO:K06629]
100339381  proliferating cell nuclear antigen [KO:K04802]
100339430  serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
100339463  S-phase kinase-associated protein 1 [KO:K03094]
100339825  DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
100339977  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100339982  ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
100340043  S-phase kinase-associated protein 1-like [KO:K03094]
100340312  anaphase-promoting complex subunit 15-like [KO:K25228]
100340619  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100340625  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
100341332  N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
100341906  membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X2 [KO:K06633] [EC:2.7.11.1]
100342116  origin recognition complex subunit 5 isoform X1 [KO:K02607]
100342147  anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
100342294  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100342311  anaphase-promoting complex subunit 10 [KO:K03357]
100342365  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100342452  S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
100342681  anaphase-promoting complex subunit 15 isoform X3 [KO:K25228]
100342694  14-3-3 protein zeta/delta [KO:K16197]
100343351  anaphase-promoting complex subunit 11 [KO:K03358]
100343390  DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
100343407  cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
100343637  M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
100343855  DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
100344311  transcription factor E2F4 [KO:K04682]
100345196  cell division cycle protein 27 homolog isoform X2 [KO:K03350]
100345230  DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
100345665  cell division cycle protein 23 homolog [KO:K03355]
100345729  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100345730  wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
100345752  cullin-1 isoform X1 [KO:K03347]
100345909  tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100346129  kinetochore scaffold 1 isoform X1 [KO:K11542]
100346294  dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100346303  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100346379  transcription factor E2F2 [KO:K09389]
100346683  MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
100346997  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
100347111  dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100347587  cohesin subunit SA-1 isoform X1 [KO:K06671]
100348036  zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
100348051  transcription factor E2F4 [KO:K04682]
100348299  anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
100348391  pachytene checkpoint protein 2 homolog [KO:K22399]
100348489  cyclin-dependent kinase inhibitor 1 [KO:K06625]
100348625  mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
100348678  wings apart-like protein homolog isoform X2 [KO:K25163]
100348842  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100348910  origin recognition complex subunit 1 [KO:K02603]
100348944  origin recognition complex subunit 6 [KO:K02608]
100348976  transcription factor E2F5 [KO:K04682]
100349099  structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
100349299  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100349461  cyclin-dependent kinase 4 inhibitor D [KO:K06623]
100349582  kinetochore protein NDC80 homolog [KO:K11547]
100349658  origin recognition complex subunit 2 isoform X2 [KO:K02604]
100349688  mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X6 [KO:K06637] [EC:2.7.11.1]
100349822  DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
100350229  anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
100350286  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
100350479  double-strand-break repair protein rad21 homolog [KO:K06670]
100351136  mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
100351717  cell division control protein 45 homolog [KO:K06628]
100351874  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100352038  histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
100352234  mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
100352301  LOW QUALITY PROTEIN: transforming growth factor beta-1 proprotein [KO:K13375]
100352365  mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
100352519  anaphase-promoting complex subunit 13 [KO:K12456]
100352668  N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
100352685  shugoshin 1 [KO:K11580]
100352785  cyclin-A2-like [KO:K06627]
100352863  cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100353173  transcription factor E2F3 isoform X1 [KO:K06620]
100353279  F-box only protein 5 [KO:K10292]
100353284  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100353300  protein DBF4 homolog B isoform X1 [KO:K06629]
100353358  MAD2L1-binding protein [KO:K26093]
100353644  sororin isoform X5 [KO:K17390]
100353742  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100354135  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100354267  mdm2-binding protein isoform X2 [KO:K26116]
100354276  14-3-3 protein gamma [KO:K16198]
100354280  M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
100354309  structural maintenance of chromosomes protein 3 [KO:K06669]
100354495  transcription factor Dp-1 [KO:K04683]
100354612  nipped-B-like protein isoform X1 [KO:K06672]
100354874  cell division cycle protein 20 homolog [KO:K03363]
100354882  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
100355092  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100355156  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100355373  LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1A-like [KO:K06636]
100355583  sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
100355758  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
100356094  sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
100356102  securin isoform X1 [KO:K06635]
100356105  separin [KO:K02365] [EC:3.4.22.49]
100356225  aurora kinase B [KO:K11479] [EC:2.7.11.1]
100356287  serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100356406  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
100356408  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100356870  securin [KO:K06635]
100356957  transcription factor E2F1 [KO:K17454]
100357094  anaphase-promoting complex subunit 11 [KO:K03358]
100357348  anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
100357416  G2/mitotic-specific cyclin-B2 [KO:K21770]
100357421  cell division control protein 6 homolog [KO:K02213]
100357431  retinoblastoma-associated protein isoform X1 [KO:K06618]
100357502  LOW QUALITY PROTEIN: fizzy-related protein homolog [KO:K03364]
100357538  pachytene checkpoint protein 2 homolog [KO:K22399]
100358091  origin recognition complex subunit 4 isoform X3 [KO:K02606]
100358179  14-3-3 protein sigma [KO:K06644]
100358276  transcription factor Dp-2 isoform X6 [KO:K09392]
100358299  14-3-3 protein beta/alpha [KO:K16197]
100358389  cyclin-A1 isoform X1 [KO:K06627]
100358645  transcriptional regulator ATRX isoform X1 [KO:K10779]
100358813  14-3-3 protein epsilon isoform X4 [KO:K06630]
100358835  anaphase-promoting complex subunit CDC26 [KO:K03359]
100358882  cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100358948  cyclin-H [KO:K06634]
100358955  cyclin-dependent kinase 4 inhibitor C [KO:K06622]
100358982  transforming growth factor beta-3 proprotein [KO:K13377]
100359062  serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
100359101  cell division cycle protein 16 homolog isoform X1 [KO:K03353]
100359137  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100359213  dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
103345448  transforming growth factor beta-1 proprotein isoform X9 [KO:K13375]
103347105  uncharacterized protein LOC103347105 [KO:K06679]
103348219  M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
103352470  E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
103352503  treslin [KO:K26117]
127482567  histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
127482835  cell division control protein 45 homolog [KO:K06628]
127483727  anaphase-promoting complex subunit 15-like [KO:K25228]
127486895  LOW QUALITY PROTEIN: anaphase-promoting complex subunit 2-like [KO:K03349]
127487420  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
127488420  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
127488492  14-3-3 protein gamma [KO:K16198]
127489175  LOW QUALITY PROTEIN: transcription factor E2F1-like [KO:K17454]
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
ocu03030  DNA replication
ocu04010  MAPK signaling pathway
ocu04120  Ubiquitin mediated proteolysis
ocu04210  Apoptosis
KO pathway
ko04110   
LinkDB

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