KEGG   PATHWAY: cpoc04110
Entry
cpoc04110                   Pathway                                
Name
Cell cycle - Cavia porcellus (domestic guinea pig)
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
cpoc04110  Cell cycle
cpoc04110

Other DBs
GO: 0000278
Organism
Cavia porcellus (domestic guinea pig) [GN:cpoc]
Gene
100729808  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
100730596  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
100718785  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100717960  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100732773  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100716297  Rb1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
100727381  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
100713872  Rbl2; LOW QUALITY PROTEIN: retinoblastoma-like protein 2 [KO:K16332]
100720976  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100728529  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100715675  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100729531  E2f1; transcription factor E2F1 [KO:K17454]
100714679  E2f2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
100722981  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
100718912  E2f5; transcription factor E2F5 [KO:K04682]
100735380  E2f4; transcription factor E2F4 isoform X1 [KO:K04682]
100725779  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
100731320  Tfdp2; transcription factor Dp-2 isoform X2 [KO:K09392]
100714392  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100135628  Tgfb1; transforming growth factor beta-1 precursor [KO:K13375]
100720726  Tgfb2; transforming growth factor beta-2 isoform X3 [KO:K13376]
100715426  Tgfb3; transforming growth factor beta-3 [KO:K13377]
100726958  Smad2; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2 [KO:K04500]
100731807  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100717853  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100724557  Myc; myc proto-oncogene protein isoform X2 [KO:K04377]
100731568  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
100731972  cyclin-dependent kinase inhibitor 2A [KO:K06621]
100732246  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100727634  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
100717134  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
100729359  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100720449  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100734034  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
100727568  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
100714324  Cdk2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100135616  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
100727053  Cul1; cullin-1 [KO:K03347]
100714763  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100720705  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
100716489  Ccna1; cyclin-A1 isoform X1 [KO:K06627]
100716947  Ccna2; cyclin-A2 [KO:K06627]
100729621  Cdc6; cell division control protein 6 homolog [KO:K02213]
100733165  Cdt1; DNA replication factor Cdt1 isoform X2 [KO:K10727]
100724157  Orc1; origin recognition complex subunit 1 [KO:K02603]
100718829  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
100727573  Orc3; origin recognition complex subunit 3 isoform X2 [KO:K02605]
100731516  Orc4; origin recognition complex subunit 4 [KO:K02606]
100727217  Orc5; LOW QUALITY PROTEIN: origin recognition complex subunit 5 [KO:K02607]
100728517  Orc6; origin recognition complex subunit 6 isoform X4 [KO:K02608]
100722936  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
100729563  Mcm3; DNA replication licensing factor MCM3 isoform X2 [KO:K02541] [EC:5.6.2.3]
100724549  Mcm4; DNA replication licensing factor MCM4 isoform X2 [KO:K02212] [EC:5.6.2.3]
100712965  Mcm5; DNA replication licensing factor MCM5 isoform X1 [KO:K02209] [EC:5.6.2.3]
100731891  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
100719227  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
100728375  Cdc45; cell division control protein 45 homolog [KO:K06628]
100728636  Ticrr; treslin [KO:K26117]
100723512  Mtbp; mdm2-binding protein isoform X1 [KO:K26116]
100716321  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
100726964  Dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
100735946  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100730790  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100720222  G2/mitotic-specific cyclin-B1 [KO:K05868]
100716328  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
100713705  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
100716851  Cdc25b; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
100727182  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
100733198  Ywhaq; 14-3-3 protein theta [KO:K16197]
100715125  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
100714396  Ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100725300  Ywhag; 14-3-3 protein gamma [KO:K16198]
100728374  Ywhah; 14-3-3 protein eta [KO:K16198]
100716866  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100726821  Wee1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
100717213  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100714526  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X3 [KO:K06633] [EC:2.7.11.1]
100726162  Ccnh; cyclin-H [KO:K06634]
100725955  Cdk7; LOW QUALITY PROTEIN: cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100725716  Anapc1; anaphase-promoting complex subunit 1 isoform X2 [KO:K03348]
100730651  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
100731091  Cdc27; cell division cycle protein 27 homolog isoform X3 [KO:K03350]
100720696  Anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
100726899  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
100725418  Cdc16; cell division cycle protein 16 homolog isoform X2 [KO:K03353]
100716878  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
100733068  Cdc23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
100728363  Anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
100734505  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
100732729  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
100728170  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
100726252  Anapc15; anaphase-promoting complex subunit 15 isoform X3 [KO:K25228]
100714226  Anapc16; anaphase-promoting complex subunit 16 isoform X3 [KO:K25229]
100718545  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
100717950  Pttg1; securin isoform X2 [KO:K06635]
100733255  Espl1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
100723138  Smc1a; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1A [KO:K06636]
100722202  Smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
100726965  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
100718361  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
100720947  Stag2; LOW QUALITY PROTEIN: cohesin subunit SA-2 [KO:K06671]
100724410  Stag1; cohesin subunit SA-1 [KO:K06671]
100715238  Atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
100731730  LOW QUALITY PROTEIN: ATP-dependent DNA helicase DDX11-like [KO:K11273] [EC:5.6.2.7]
100718018  Ddx11; ATP-dependent DNA helicase DDX11 isoform X3 [KO:K11273] [EC:5.6.2.7]
100718118  Nipbl; LOW QUALITY PROTEIN: nipped-B-like protein [KO:K06672]
100718568  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
100721893  Hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
100735054  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101787413  Esco1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
100714247  Pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
100716646  Pds5a; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
100726455  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
100728918  LOW QUALITY PROTEIN: wings apart-like protein homolog [KO:K25163]
100724921  sororin [KO:K17390]
100727564  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
100718738  Sgo1; shugoshin 1 [KO:K11580]
100724172  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
100720727  Ppp2cb; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100713478  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100734047  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
100732627  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
100727229  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
100735391  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
100723199  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
100723810  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100717899  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
100730663  Knl1; kinetochore scaffold 1 [KO:K11542]
100723582  Ttk; LOW QUALITY PROTEIN: dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
100731466  Mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
100731050  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
100716735  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
100728730  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
100735802  Bub3; mitotic checkpoint protein BUB3 [KO:K02180]
100725012  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
100733277  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
100731857  Mad2l1bp; MAD2L1-binding protein [KO:K26093]
100714794  Fzr1; fizzy-related protein homolog [KO:K03364]
100714021  Fbxo5; F-box only protein 5 [KO:K10292]
100727486  Cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100722401  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100716770  Crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100734820  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100724826  Prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
100732693  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
100717983  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100724684  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100379269  Tp53; cellular tumor antigen p53 [KO:K04451]
100719739  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100730773  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100713865  Pcna; proliferating cell nuclear antigen [KO:K04802]
100727402  Sfn; 14-3-3 protein sigma [KO:K06644]
100719613  Chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100727440  Chek2; serine/threonine-protein kinase Chk2 isoform X2 [KO:K06641] [EC:2.7.11.1]
100721008  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.
  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
cpoc03030  DNA replication
cpoc04010  MAPK signaling pathway
cpoc04120  Ubiquitin mediated proteolysis
cpoc04210  Apoptosis
KO pathway
ko04110   
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