KEGG   PATHWAY: mcoc04110
Entry
mcoc04110                   Pathway                                
Name
Cell cycle - Mastomys coucha (southern multimammate mouse)
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
mcoc04110  Cell cycle
mcoc04110

Other DBs
GO: 0000278
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116068051  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
116068143  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
116068366  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
116068375  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
116068447  Tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
116068539  [KO:K16197]
116068554  Ywhag; 14-3-3 protein gamma [KO:K16198]
116068616  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
116068664  Mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
116068818  Pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
116068891  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
116068936  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
116068942  Cdc16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
116069440  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
116069587  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
116069632  Anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
116069761  Orc6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
116069796  Ywhah; 14-3-3 protein eta [KO:K16198]
116069845  Rbl2; retinoblastoma-like protein 2 [KO:K16332]
116070042  E2f4; transcription factor E2F4 [KO:K04682]
116070336  Cdt1; DNA replication factor Cdt1 [KO:K10727]
116071067  Pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
116071915  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
116072023  Ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
116072034  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
116072586  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
116072801  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
116073048  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
116073193  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
116073222  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
116073310  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
116073895  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
116073909  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
116073956  Stag1; cohesin subunit SA-1 [KO:K06671]
116074400  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
116074686  Sgo1; shugoshin 1 isoform X1 [KO:K11580]
116074757  Mad2l1bp; MAD2L1-binding protein [KO:K26093]
116074873  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
116075067  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
116075178  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
116075461  Anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
116075523  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
116075684  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
116075863  Fzr1; fizzy-related protein homolog [KO:K03364]
116075868  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116075923  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
116076163  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
116076358  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
116076368  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116076823  Cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
116077116  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
116077277  Smc1b; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
116077586  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
116077615  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
116078150  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
116078246  Skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
116078411  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
116078418  Fbxo5; F-box only protein 5 isoform X1 [KO:K10292]
116078461  Cdc6; cell division control protein 6 homolog [KO:K02213]
116078542  Pttg1; securin [KO:K06635]
116078815  Ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
116079262  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
116079782  Ywhaq; 14-3-3 protein theta [KO:K16197]
116080027  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
116080097  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
116080433  Espl1; separin [KO:K02365] [EC:3.4.22.49]
116080458  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
116081456  Mtbp; mdm2-binding protein isoform X1 [KO:K26116]
116081480  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
116081542  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116081717  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
116081743  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116081762  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
116082253  Myc; myc proto-oncogene protein [KO:K04377]
116083126  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
116083200  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
116083410  Ccnh; cyclin-H isoform X1 [KO:K06634]
116083582  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
116083719  Cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
116083772  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
116084103  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
116084175  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116085075  Rb1; retinoblastoma-associated protein [KO:K06618]
116085359  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
116085621  Prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
116085622  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
116085700  Cdc45; cell division control protein 45 homolog [KO:K06628]
116085894  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116086836  Esco1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
116086976  Cdc23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
116086979  Cdc25c; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
116087308  Hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
116087335  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
116087365  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
116087903  Atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
116087970  Orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
116088079  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
116088225  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
116088461  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
116088858  Ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
116088898  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
116089805  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
116089830  Smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
116089976  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
116090147  Orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
116090691  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
116090708  Knl1; kinetochore scaffold 1 isoform X1 [KO:K11542]
116090892  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
116090900  Anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
116090957  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
116090975  Pcna; proliferating cell nuclear antigen [KO:K04802]
116091213  E2f1; transcription factor E2F1 [KO:K17454]
116091283  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
116091328  Stag2; cohesin subunit SA-2 [KO:K06671]
116091353  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
116091552  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
116092877  Ccna1; cyclin-A1 isoform X1 [KO:K06627]
116092994  [KO:K10779]
116093677  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116094951  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
116095103  Ccna2; cyclin-A2 [KO:K06627]
116095785  E2f2; transcription factor E2F2 [KO:K09389]
116096104  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
116096224  [KO:K06621]
116096225  Cdkn2b; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
116096379  Orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
116096405  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
116096523  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
116096707  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
116096961  Zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
116097011  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
116097440  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
116097471  Dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
116097526  Orc5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
116098016  [KO:K06644]
116098059  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
116098531  Cul1; cullin-1 [KO:K03347]
116098617  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
116099015  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
116099018  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116099232  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
116099629  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
116099702  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116101857  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
116102054  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
116102439  Ticrr; treslin [KO:K26117]
116102686  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
116102789  Wee1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
116102914  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
116103102  Bub3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
116103262  Cdkn1c; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
116103285  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
116103433  Cdca5; LOW QUALITY PROTEIN: sororin [KO:K17390]
116103440  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
116104001  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
116104531  Anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
116104772  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
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
mcoc03030  DNA replication
mcoc04010  MAPK signaling pathway
mcoc04120  Ubiquitin mediated proteolysis
mcoc04210  Apoptosis
KO pathway
ko04110   

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