KEGG   PATHWAY: mpah04110
Entry
mpah04110                   Pathway                                
Name
Cell cycle - Mus pahari (shrew 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
mpah04110  Cell cycle
mpah04110

Other DBs
GO: 0000278
Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110322378  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
110315929  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110335402  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
110326196  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
110316496  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
110325233  Rb1; retinoblastoma-associated protein [KO:K06618]
110318208  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
110337191  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
110318646  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
110326229  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
110322864  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
110318578  E2f1; transcription factor E2F1 [KO:K17454]
110323461  E2f2; transcription factor E2F2 [KO:K09389]
110333784  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
110320211  E2f5; transcription factor E2F5 [KO:K04682]
110337449  E2f4; transcription factor E2F4 [KO:K04682]
110336946  Tfdp1; transcription factor Dp-1 [KO:K04683]
110327334  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
110329614  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
110336543  Tgfb1; transforming growth factor beta-1 isoform X1 [KO:K13375]
110321649  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
110324521  Tgfb3; transforming growth factor beta-3 [KO:K13377]
110332834  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110327577  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110333204  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
110334656  Myc; myc proto-oncogene protein [KO:K04377]
110322947  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
110323545  cyclin-dependent kinase inhibitor 2A [KO:K06621]
110323643  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110323411  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
110328024  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
110316560  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110331201  Cdkn1c; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
110338236  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
110338930  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110324083  Ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
110327130  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110331774  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
110316251  Cul1; cullin-1 [KO:K03347]
110334961  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
110328844  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
110320587  Ccna1; cyclin-A1 [KO:K06627]
110320068  Ccna2; cyclin-A2 [KO:K06627]
110331962  Cdc6; cell division control protein 6 homolog [KO:K02213]
110337557  Cdt1; DNA replication factor Cdt1 [KO:K10727]
110323323  Orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
110321380  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
110338708  Orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
110318512  Orc4; origin recognition complex subunit 4 [KO:K02606]
110316018  Orc5; origin recognition complex subunit 5 [KO:K02607]
110337785  Orc6; origin recognition complex subunit 6 [KO:K02608]
110314858  Mcm2; DNA replication licensing factor MCM2 isoform X1 [KO:K02540] [EC:5.6.2.3]
110321301  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
110329521  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
110336228  Mcm5; DNA replication licensing factor MCM5 isoform X1 [KO:K02209] [EC:5.6.2.3]
110321456  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
110339113  Mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
110329379  Cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
110321908  Ticrr; treslin isoform X1 [KO:K26117]
110334880  Mtbp; mdm2-binding protein [KO:K26116]
110330378  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
110314632  protein DBF4 homolog A-like [KO:K06629]
110326492  Cdk1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
110328828  Ccnb1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
110327463  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
110313711  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
110318116  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
110333485  Cdc25c; LOW QUALITY PROTEIN: M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
110318313  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
110313584  LOW QUALITY PROTEIN: 14-3-3 protein zeta/delta-like [KO:K16197]
110324236  Ywhaq; LOW QUALITY PROTEIN: 14-3-3 protein theta [KO:K16197]
110331575  Ywhae; 14-3-3 protein epsilon [KO:K06630]
110312793  Ywhag; 14-3-3 protein gamma [KO:K16198]
110330275  Ywhah; 14-3-3 protein eta [KO:K16198]
110319327  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
110316986  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
110327263  Wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
110338115  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
110328945  Ccnh; cyclin-H isoform X1 [KO:K06634]
110328829  Cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
110318008  Anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
110318457  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
110331459  Cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
110331043  Anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
110339048  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
110336947  Cdc16; cell division cycle protein 16 homolog [KO:K03353]
110313144  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
110333212  Cdc23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
110337550  Anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
110332424  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
110323594  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
110327467  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
110338331  anaphase-promoting complex subunit 15-like [KO:K25228]
110316534  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
110326413  Anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
110322771  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
110332496  Pttg1; securin [KO:K06635]
110334838  Espl1; separin [KO:K02365] [EC:3.4.22.49]
110313280  Smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
110334947  Smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
110322004  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
110334800  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
110328521  Stag1; cohesin subunit SA-1 [KO:K06671]
110313785  Stag2; cohesin subunit SA-2 [KO:K06671]
110313841  Atrx; transcriptional regulator ATRX [KO:K10779]
110335669  Ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
110328825  Nipbl; nipped-B-like protein [KO:K06672]
110336316  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
110313451  Hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
110325717  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
110333276  Esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
110330421  Pds5a; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
110339026  Pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
110326029  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
110333773  Cdca5; sororin [KO:K17390]
110331779  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
110335929  Sgo1; shugoshin 1 [KO:K11580]
110336304  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
110331422  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
110328279  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
110337932  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
110321572  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
110321059  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
110324840  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
110324283  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
110335699  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
110335692  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
110318212  Knl1; kinetochore scaffold 1 [KO:K11542]
110327588  Ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
110312757  Mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
110316490  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
110322837  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
110318363  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
110320086  Bub3; mitotic checkpoint protein BUB3 [KO:K02180]
110317716  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
110328939  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
110336081  Mad2l1bp; MAD2L1-binding protein [KO:K26093]
110326218  Fzr1; fizzy-related protein homolog isoform X1 [KO:K03364]
110338210  Fbxo5; F-box only protein 5 [KO:K10292]
110319906  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
110333592  Cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
110334526  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110330048  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110330004  Prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
110327928  Atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
110327456  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
110326473  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
110331731  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110316550  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
110326839  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110333844  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110318283  Pcna; proliferating cell nuclear antigen isoform X1 [KO:K04802]
110323250  Sfn; 14-3-3 protein sigma [KO:K06644]
110327308  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
110312870  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
110327415  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
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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.
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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
mpah03030  DNA replication
mpah04010  MAPK signaling pathway
mpah04120  Ubiquitin mediated proteolysis
mpah04210  Apoptosis
KO pathway
ko04110   
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