KEGG   PATHWAY: mmu04110
Entry
mmu04110                    Pathway                                
Name
Cell cycle - Mus musculus (house 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
mmu04110  Cell cycle
mmu04110

Other DBs
GO: 0000278
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
100039786  Gm2423; predicted gene 2423 [KO:K16197]
100710  Pds5b; PDS5 cohesin associated factor B [KO:K11267]
104394  E2f4; E2F transcription factor 4 [KO:K04682]
105837  Mtbp; Mdm2, transformed 3T3 cell double minute p53 binding protein [KO:K26116]
105988  Espl1; extra spindle pole bodies 1, separase [KO:K02365] [EC:3.4.22.49]
107995  Cdc20; cell division cycle 20 [KO:K03363]
11350  Abl1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
11920  Atm; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
12235  Bub1; BUB1, mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
12236  Bub1b; BUB1B, mitotic checkpoint serine/threonine kinase [KO:K06637] [EC:2.7.11.1]
12237  Bub3; BUB3 mitotic checkpoint protein [KO:K02180]
12427  Ccna1; cyclin A1 [KO:K06627]
12428  Ccna2; cyclin A2 [KO:K06627]
12442  Ccnb2; cyclin B2 [KO:K21770]
12443  Ccnd1; cyclin D1 [KO:K04503]
12444  Ccnd2; cyclin D2 [KO:K10151]
12445  Ccnd3; cyclin D3 [KO:K10152]
12447  Ccne1; cyclin E1 [KO:K06626]
12448  Ccne2; cyclin E2 [KO:K06626]
12530  Cdc25a; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
12531  Cdc25b; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
12532  Cdc25c; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
12534  Cdk1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
12544  Cdc45; cell division cycle 45 [KO:K06628]
12545  Cdc7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
12566  Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
12567  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
12572  Cdk7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
12575  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
12576  Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624]
12577  Cdkn1c; cyclin dependent kinase inhibitor 1C [KO:K09993]
12578  Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621]
12579  Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685]
12580  Cdkn2c; cyclin dependent kinase inhibitor 2C [KO:K06622]
12581  Cdkn2d; cyclin dependent kinase inhibitor 2D [KO:K06623]
12649  Chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
12914  Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
13006  Smc3; structural maintenance of chromosomes 3 [KO:K06669]
13197  Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
13559  E2f5; E2F transcription factor 5 [KO:K04682]
140557  Smc1b; structural maintenance of chromosomes 1B [KO:K06636]
15182  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
17120  Mad1l1; MAD1 mitotic arrest deficient 1-like 1 [KO:K06679]
17126  Smad2; SMAD family member 2 [KO:K04500]
17127  Smad3; SMAD family member 3 [KO:K23605]
17128  Smad4; SMAD family member 4 [KO:K04501]
17215  Mcm3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
17216  Mcm2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
17217  Mcm4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
17218  Mcm5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
17219  Mcm6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
17220  Mcm7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
17222  Anapc1; anaphase promoting complex subunit 1 [KO:K03348]
17246  Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
17873  Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
18392  Orc1; origin recognition complex, subunit 1 [KO:K02603]
18393  Orc2; origin recognition complex, subunit 2 [KO:K02604]
18538  Pcna; proliferating cell nuclear antigen [KO:K04802]
18817  Plk1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:3.1.3.16]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
19090  Prkdc; protein kinase, DNA activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
19357  Rad21; RAD21 cohesin complex component [KO:K06670]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
19650  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
19651  Rbl2; RB transcriptional corepressor like 2 [KO:K16332]
20842  Stag1; STAG1 cohesin complex component [KO:K06671]
20843  Stag2; STAG2 cohesin complex component [KO:K06671]
20877  Aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
209091  Ccnb3; cyclin B3 [KO:K21771]
211586  Tfdp2; transcription factor Dp 2 [KO:K09392]
21402  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
217232  Cdc27; cell division cycle 27 [KO:K03350]
21770  Ppp2r5d; protein phosphatase 2, regulatory subunit B', delta [KO:K11584]
21781  Tfdp1; transcription factor Dp 1 [KO:K04683]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [KO:K13377]
218294  Cdc14b; CDC14 cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
218914  Wapl; WAPL cohesin release factor [KO:K25163]
22059  Trp53; transformation related protein 53 [KO:K04451]
22137  Ttk; Ttk protein kinase [KO:K08866] [EC:2.7.12.1]
22390  Wee1; WEE 1 homolog 1 (S. pombe) [KO:K06632] [EC:2.7.11.1]
225849  Ppp2r5b; protein phosphatase 2, regulatory subunit B', beta [KO:K11584]
22589  Atrx; ATRX, chromatin remodeler [KO:K10779]
22627  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
22628  Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide [KO:K16198]
22629  Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide [KO:K16198]
22630  Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
22631  Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide [KO:K16197]
22642  Zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
226849  Ppp2r5a; protein phosphatase 2, regulatory subunit B', alpha [KO:K11584]
229776  Cdc14a; CDC14 cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
23834  Cdc6; cell division cycle 6 [KO:K02213]
23882  Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
24061  Smc1a; structural maintenance of chromosomes 1A [KO:K06636]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
245000  Atr; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
26428  Orc4; origin recognition complex, subunit 4 [KO:K02606]
26429  Orc5; origin recognition complex, subunit 5 [KO:K02607]
268697  Ccnb1; cyclin B1 [KO:K05868]
268930  Pkmyt1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
26931  Ppp2r5c; protein phosphatase 2, regulatory subunit B', gamma [KO:K11584]
26932  Ppp2r5e; protein phosphatase 2, regulatory subunit B', epsilon [KO:K11584]
26965  Cul1; cullin 1 [KO:K03347]
27214  Dbf4; DBF4 zinc finger [KO:K06629]
27401  Skp2; S-phase kinase-associated protein 2 [KO:K03875]
30939  Pttg1; pituitary tumor-transforming gene 1 [KO:K06635]
320209  Ddx11; DEAD/H box helicase 11 [KO:K11273] [EC:5.6.2.7]
328572  Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
381759  Wee2; WEE1 homolog 2 (S. pombe) [KO:K06632] [EC:2.7.11.1]
433759  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
434175  Ccnb1-ps; cyclin B1, pseudogene [KO:K05868]
50793  Orc3; origin recognition complex, subunit 3 [KO:K02605]
50883  Chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
52206  Anapc4; anaphase promoting complex subunit 4 [KO:K03351]
52563  Cdc23; CDC23 cell division cycle 23 [KO:K03355]
52717  Anapc16; anaphase promoting complex subunit 16 [KO:K25229]
54401  Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide [KO:K16197]
55948  Sfn; stratifin [KO:K06644]
56150  Mad2l1; MAD2 mitotic arrest deficient-like 1 [KO:K02537]
56317  Anapc7; anaphase promoting complex subunit 7 [KO:K03354]
56371  Fzr1; fizzy and cell division cycle 20 related 1 [KO:K03364]
56438  Rbx1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
56452  Orc6; origin recognition complex, subunit 6 [KO:K02608]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
59008  Anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
66156  Anapc11; anaphase promoting complex subunit 11 [KO:K03358]
66440  Cdc26; cell division cycle 26 [KO:K03359]
66591  Mad2l1bp; MAD2L1 binding protein [KO:K26093]
66671  Ccnh; cyclin H [KO:K06634]
67052  Ndc80; NDC80 kinetochore complex component [KO:K11547]
67141  Fbxo5; F-box protein 5 [KO:K10292]
67177  Cdt1; chromatin licensing and DNA replication factor 1 [KO:K10727]
67849  Cdca5; cell division cycle associated 5 [KO:K17390]
68999  Anapc10; anaphase promoting complex subunit 10 [KO:K03357]
69010  Anapc13; anaphase promoting complex subunit 13 [KO:K12456]
69716  Trip13; thyroid hormone receptor interactor 13 [KO:K22399]
69957  Cdc16; CDC16 cell division cycle 16 [KO:K03353]
70315  Hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
71175  Nipbl; NIPBL cohesin loading factor [KO:K06672]
71521  Pds5a; PDS5 cohesin associated factor A [KO:K11267]
71890  Mad2l2; MAD2 mitotic arrest deficient-like 2 [KO:K13728]
71988  Esco2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
72415  Sgo1; shugoshin 1 [KO:K11580]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
74549  Mau2; MAU2 sister chromatid cohesion factor [KO:K11266]
75430  Anapc15; anaphase promoting complex C subunit 15 [KO:K25228]
76464  Knl1; kinetochore scaffold 1 [KO:K11542]
77011  Ticrr; TOPBP1-interacting checkpoint and replication regulator [KO:K26117]
77805  Esco1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
99152  Anapc2; anaphase promoting complex subunit 2 [KO:K03349]
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
mmu03030  DNA replication
mmu04010  MAPK signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04210  Apoptosis
KO pathway
ko04110   

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