KEGG   PATHWAY: mun04110
Entry
mun04110                    Pathway                                
Name
Cell cycle - Meriones unguiculatus (Mongolian gerbil)
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
mun04110  Cell cycle
mun04110

Other DBs
GO: 0000278
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110539454  Orc4; origin recognition complex subunit 4 [KO:K02606]
110539531  Atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
110539810  Dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
110539931  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
110540768  [KO:K11273] [EC:3.6.4.13]
110540818  Smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
110541702  Stag1; cohesin subunit SA-1 [KO:K06671]
110542420  Stag2; cohesin subunit SA-2 isoform X1 [KO:K06671]
110542979  Ccnb3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
110544860  Zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
110545048  Smc1b; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
110545202  Cdt1; DNA replication factor Cdt1 [KO:K10727]
110545320  Anapc7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
110545327  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
110545357  Trip13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
110545385  E2f2; transcription factor E2F2 [KO:K09389]
110545634  Cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
110545636  E2f4; transcription factor E2F4 isoform X1 [KO:K04682]
110545702  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110545930  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
110545943  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110546448  Ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110546732  Cdkn1c; cyclin-dependent kinase inhibitor 1C isoform X4 [KO:K09993]
110546940  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
110547488  Ywhae; 14-3-3 protein epsilon [KO:K06630]
110547501  Cul1; cullin-1 [KO:K03347]
110547832  Anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
110548020  Wapl; wings apart-like protein homolog isoform X2 [KO:K25163]
110548200  Wee1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
110548204  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
110548219  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
110548295  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
110548328  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
110548514  Fzr1; fizzy-related protein homolog [KO:K03364]
110548554  Hdac1; histone deacetylase 1 isoform X2 [KO:K06067] [EC:3.5.1.98]
110548628  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110548824  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
110549077  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
110549177  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
110549244  Tgfb2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
110549337  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
110549352  Cdca5; sororin [KO:K17390]
110549439  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
110549468  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
110549625  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
110549633  Skp1; S-phase kinase-associated protein 1 isoform X2 [KO:K03094]
110549889  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
110550225  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
110550301  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110550356  Mad2l1bp; MAD2L1-binding protein [KO:K26093]
110550362  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
110550435  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
110550606  Knl1; kinetochore scaffold 1 [KO:K11542]
110550653  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
110550715  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
110551008  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110551292  Cdc16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
110551399  Anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
110551710  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
110551845  Orc3; origin recognition complex subunit 3 isoform X4 [KO:K02605]
110551870  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
110552292  Anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
110552298  Espl1; separin [KO:K02365] [EC:3.4.22.49]
110552626  Sfn; 14-3-3 protein sigma [KO:K06644]
110552922  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
110552990  Orc6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
110553166  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
110553236  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
110553345  Cdc45; cell division control protein 45 homolog [KO:K06628]
110553592  Rb1; retinoblastoma-associated protein [KO:K06618]
110554089  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110554299  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
110554385  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110554386  [KO:K06621]
110554547  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110554804  Orc5; origin recognition complex subunit 5 [KO:K02607]
110554919  Ccna1; cyclin-A1 [KO:K06627]
110555127  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110555292  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
110555373  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
110555416  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
110555453  Pttg1; securin [KO:K06635]
110555570  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
110555604  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110555709  Cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
110555755  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B isoform X2 [KO:K13728]
110555762  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
110555864  Ywhag; 14-3-3 protein gamma [KO:K16198]
110556264  [KO:K12456]
110556336  Mtbp; mdm2-binding protein isoform X1 [KO:K26116]
110556831  [KO:K25228]
110556971  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
110557011  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
110557028  Pcna; proliferating cell nuclear antigen [KO:K04802]
110557450  Ywhah; 14-3-3 protein eta [KO:K16198]
110557542  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
110557573  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
110557660  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
110557678  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
110557887  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110558214  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
110558230  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
110558380  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
110558390  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
110558423  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
110558426  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
110558466  Cdc25c; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
110558470  Cdc23; cell division cycle protein 23 homolog [KO:K03355]
110558508  Cdc6; cell division control protein 6 homolog isoform X1 [KO:K02213]
110558702  Anapc4; anaphase-promoting complex subunit 4 [KO:K03351]
110558718  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
110558790  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
110558915  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
110559073  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110559282  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X2 [KO:K02178] [EC:2.7.11.1]
110559398  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110559403  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
110559622  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
110559633  Ccna2; cyclin-A2 isoform X1 [KO:K06627]
110559981  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
110560064  Myc; myc proto-oncogene protein [KO:K04377]
110560607  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
110560718  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
110560855  Ccnb2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
110560863  Sgo1; shugoshin 1 [KO:K11580]
110561197  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110561220  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
110561245  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
110561277  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110561334  Prkdc; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
110561337  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
110561800  E2f3; transcription factor E2F3 isoform X3 [KO:K06620]
110562051  Pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
110562225  Ticrr; treslin [KO:K26117]
110562241  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
110563235  E2f5; transcription factor E2F5 [KO:K04682]
110563514  Orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
110563557  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
110564076  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
110564212  Ywhaq; 14-3-3 protein theta [KO:K16197]
110564354  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
110564463  Ccnh; cyclin-H isoform X1 [KO:K06634]
110564486  Fbxo5; F-box only protein 5 isoform X1 [KO:K10292]
110564693  Bub3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
110565221  Hdac8; histone deacetylase 8 isoform X2 [KO:K11405] [EC:3.5.1.98]
110565703  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
110565748  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
110566051  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
110566170  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
110566173  Cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
110566281  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
110566837  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
110566924  Esco1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
132650551  Pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
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
mun03030  DNA replication
mun04010  MAPK signaling pathway
mun04120  Ubiquitin mediated proteolysis
mun04210  Apoptosis
KO pathway
ko04110   

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