KEGG   PATHWAY: ccan04110
Entry
ccan04110                   Pathway                                
Name
Cell cycle - Castor canadensis (American beaver)
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
ccan04110  Cell cycle
ccan04110

Other DBs
GO: 0000278
Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109674545  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109674834  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
109674904  Sgo1; shugoshin 1 [KO:K11580]
109675312  [KO:K06679]
109675345  [KO:K06679]
109675480  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
109675992  [KO:K10779]
109676406  [KO:K02537]
109677151  Orc5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
109677666  Ccna1; cyclin-A1 [KO:K06627]
109677835  Knl1; protein CASC5 [KO:K11542]
109679711  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
109681358  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
109681430  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
109681582  Ywhag; 14-3-3 protein gamma [KO:K16198]
109681682  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109681732  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
109681793  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
109681820  Ccna2; cyclin-A2 [KO:K06627]
109682075  Mad2l1bp; MAD2L1-binding protein [KO:K26093]
109682077  [KO:K04682]
109682148  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
109682157  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109682328  Wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
109682372  Orc6; origin recognition complex subunit 6 [KO:K02608]
109682601  Ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109682631  Anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
109682730  Hdac2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
109683205  Cdc14b; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109683617  [KO:K02178] [EC:2.7.11.1]
109683941  Stag1; cohesin subunit SA-1 isoform X1 [KO:K06671]
109684045  Espl1; separin [KO:K02365] [EC:3.4.22.49]
109684110  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
109684316  Cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
109684543  Pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
109684544  [KO:K11267]
109684667  [KO:K02091] [EC:2.7.11.22]
109684671  [KO:K02091] [EC:2.7.11.22]
109684772  Wapl; wings apart-like protein homolog [KO:K25163]
109685333  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
109685456  Anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
109685632  Tgfb1; transforming growth factor beta-1 [KO:K13375]
109685702  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
109685708  [KO:K02202] [EC:2.7.11.22 2.7.11.23]
109685710  [KO:K02202] [EC:2.7.11.22 2.7.11.23]
109686152  Tgfb3; transforming growth factor beta-3 [KO:K13377]
109686224  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
109686471  Orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
109686632  [KO:K21771]
109686633  [KO:K21771]
109686914  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109686939  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
109686942  Cdc16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
109686959  Pttg1; LOW QUALITY PROTEIN: securin [KO:K06635]
109687032  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
109687049  Fzr1; fizzy-related protein homolog [KO:K03364]
109687100  Cdca5; sororin [KO:K17390]
109687165  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
109687389  Anapc2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
109687546  Ticrr; LOW QUALITY PROTEIN: treslin [KO:K26117]
109687790  Ppp2r1b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109688156  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
109688163  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109688170  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109688460  [KO:K10151]
109688461  [KO:K10151]
109688494  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
109688672  Prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
109688673  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
109688690  Anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
109688748  Anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
109688945  Orc1; origin recognition complex subunit 1 [KO:K02603]
109689058  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
109689203  Orc4; origin recognition complex subunit 4 [KO:K02606]
109689481  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
109689490  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109689797  Cdkn1c; cyclin-dependent kinase inhibitor 1C [KO:K09993]
109689828  Pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
109690250  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
109690309  Mtbp; mdm2-binding protein [KO:K26116]
109690498  [KO:K21771]
109690638  [KO:K11405] [EC:3.5.1.98]
109690765  E2f1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
109690781  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
109690951  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109691045  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109691094  Rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
109691288  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
109691394  Dbf4b; protein DBF4 homolog B [KO:K06629]
109691504  Smc3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
109691549  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
109691643  Bub3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
109691659  [KO:K02087] [EC:2.7.11.22 2.7.11.23]
109691712  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
109692163  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109692311  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
109692532  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
109692558  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
109692770  Cdt1; DNA replication factor Cdt1 [KO:K10727]
109692955  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
109692991  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
109693011  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
109693086  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
109693333  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
109693520  Bub1b; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
109693733  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
109693815  [KO:K09389]
109693824  E2f2; transcription factor E2F2 [KO:K09389]
109693840  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
109693890  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
109694031  E2f4; transcription factor E2F4 [KO:K04682]
109694044  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
109694423  Cdc6; cell division control protein 6 homolog isoform X1 [KO:K02213]
109694625  Ccnh; cyclin-H [KO:K06634]
109695112  [KO:K02087] [EC:2.7.11.22 2.7.11.23]
109695151  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
109695511  Cul1; cullin-1 [KO:K03347]
109695602  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
109695677  Pcna; proliferating cell nuclear antigen [KO:K04802]
109695924  Ywhaq; 14-3-3 protein theta [KO:K16197]
109696020  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
109696351  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109696503  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
109696587  Cdc27; cell division cycle protein 27 homolog [KO:K03350]
109696612  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
109697109  [KO:K11273] [EC:3.6.4.13]
109697135  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
109697329  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
109697654  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
109697789  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
109698008  Ttk; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
109698312  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109698488  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
109698572  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
109698650  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109698746  Sfn; 14-3-3 protein sigma [KO:K06644]
109699005  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
109699056  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
109699142  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
109699227  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
109699358  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109699559  [KO:K10779]
109699641  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
109699748  [KO:K06636]
109699749  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
109699835  Atr; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
109699943  Myc; myc proto-oncogene protein [KO:K04377]
109700012  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
109700177  Cdc23; cell division cycle protein 23 homolog [KO:K03355]
109700186  Cdc25c; LOW QUALITY PROTEIN: M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
109700215  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
109700228  Stag2; cohesin subunit SA-2 [KO:K06671]
109700302  [KO:K04500]
109700303  Chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
109700581  Cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
109700917  Ywhah; 14-3-3 protein eta [KO:K16198]
109701025  Esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
109701107  [KO:K06621]
109701109  [KO:K04685]
109701269  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
109701324  Dbf4; protein DBF4 homolog A [KO:K06629]
109701468  Fbxo5; F-box only protein 5 [KO:K10292]
109701514  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
109702014  [KO:K06636]
109702695  Skp2; S-phase kinase-associated protein 2 [KO:K03875]
109702991  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
109702994  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
109703185  [KO:K02537]
109703232  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
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)
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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)
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Reference
PMID:12573239
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
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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)
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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)
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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
ccan03030  DNA replication
ccan04010  MAPK signaling pathway
ccan04120  Ubiquitin mediated proteolysis
ccan04210  Apoptosis
KO pathway
ko04110   

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