KEGG   PATHWAY: mpuf04110
Entry
mpuf04110                   Pathway                                
Name
Cell cycle - Mustela putorius furo (domestic ferret)
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
mpuf04110  Cell cycle
mpuf04110

Other DBs
GO: 0000278
Organism
Mustela putorius furo (domestic ferret) [GN:mpuf]
Gene
101670844  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101684525  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101689940  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101673063  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101693655  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101685420  RB1; retinoblastoma-associated protein [KO:K06618]
101673051  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101670573  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101689921  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
101680954  HDAC2; histone deacetylase 2 isoform X2 [KO:K06067] [EC:3.5.1.98]
101681953  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101681681  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
101678713  E2F2; transcription factor E2F2 [KO:K09389]
101693488  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101692671  E2F4; transcription factor E2F4 [KO:K04682]
101689271  E2F5; transcription factor E2F5 [KO:K04682]
101690221  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
101673854  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
101692999  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101670127  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
101677182  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
101678400  TGFB3; transforming growth factor beta-3 [KO:K13377]
101691860  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101677980  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101675099  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101689754  MYC; myc proto-oncogene protein isoform X3 [KO:K04377]
101684746  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
101672555  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
101672835  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101673844  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101677636  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101688289  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101671066  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101676647  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101683624  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101675892  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
101682868  S-phase kinase-associated protein 1 [KO:K03094]
101687227  LOW QUALITY PROTEIN: uncharacterized protein LOC101687227 [KO:K03347]
101684109  CUL1; cullin-1 [KO:K03347]
101687674  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101682622  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
101680443  CCNA1; cyclin-A1 isoform X2 [KO:K06627]
101677173  CCNA2; cyclin-A2 [KO:K06627]
101684477  CDC6; cell division control protein 6 homolog [KO:K02213]
101683563  CDT1; DNA replication factor Cdt1 [KO:K10727]
101689494  ORC1; origin recognition complex subunit 1 [KO:K02603]
101672067  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
101693160  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
101686292  ORC4; origin recognition complex subunit 4 [KO:K02606]
101689648  ORC5; origin recognition complex subunit 5 isoform X2 [KO:K02607]
101672763  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
101692554  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101671802  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
101685899  MCM4; DNA replication licensing factor MCM4 isoform X1 [KO:K02212] [EC:5.6.2.3]
101676064  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101683757  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101672914  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101689950  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
101685328  TICRR; treslin isoform X1 [KO:K26117]
101693418  MTBP; mdm2-binding protein [KO:K26116]
101688462  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
101690200  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
101675694  DBF4B; protein DBF4 homolog B isoform X2 [KO:K06629]
101674179  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101683116  CCNB1; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1 [KO:K05868]
101691234  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1-like [KO:K05868]
101670335  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101671422  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
101683753  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
101678023  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
101679932  YWHAQ; 14-3-3 protein theta [KO:K16197]
101687663  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
101670406  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101684776  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101673417  YWHAG; 14-3-3 protein gamma [KO:K16198]
101676561  YWHAH; 14-3-3 protein eta [KO:K16198]
101674418  PLK1; serine/threonine-protein kinase PLK1 isoform X1 [KO:K06631] [EC:2.7.11.21]
101675500  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
101669959  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101675076  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
101691610  CCNH; cyclin-H isoform X1 [KO:K06634]
101681853  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101687672  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
101686101  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101676686  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
101684946  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
101687600  ANAPC5; anaphase-promoting complex subunit 5 isoform X2 [KO:K03352]
101686422  CDC16; cell division cycle protein 16 homolog [KO:K03353]
101690928  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
101680528  CDC23; cell division cycle protein 23 homolog [KO:K03355]
101677680  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
101674396  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
101680241  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
101672178  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101692406  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
101682251  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
101672474  CDC20; cell division cycle protein 20 homolog [KO:K03363]
101672114  securin-like [KO:K06635]
101685404  securin [KO:K06635]
101693864  PTTG1; securin isoform X1 [KO:K06635]
101682674  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
101674674  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
101693771  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
101670273  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
101690137  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
101693970  STAG1; cohesin subunit SA-1 [KO:K06671]
101675162  cohesin subunit SA-2-like isoform X1 [KO:K06671]
101669873  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
101672892  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
101692332  DDX11; probable ATP-dependent RNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
101679892  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
101682039  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101691321  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101673233  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
101692805  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101686431  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
101688318  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
101683121  WAPAL; wings apart-like protein homolog isoform X1 [KO:K25163]
101670098  CDCA5; sororin [KO:K17390]
101692548  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
101684815  SGOL1; shugoshin-like 1 [KO:K11580]
101671650  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101686724  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101691050  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
101678665  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X6 [KO:K11584]
101673249  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
101679697  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101671266  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101677587  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101689850  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
101679150  CASC5; protein CASC5 isoform X1 [KO:K11542]
101675505  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
101693933  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
101679727  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101672277  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101671914  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
101671723  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
101682952  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
101677546  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
101689649  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
101694007  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
101693747  FBXO5; F-box only protein 5 [KO:K10292]
101683771  CDC14B; dual specificity protein phosphatase CDC14B isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101684230  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101686721  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101681230  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101687340  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
101670820  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
101673428  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101689782  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101677794  TP53; cellular tumor antigen p53 [KO:K04451]
101674139  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101693694  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101678248  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101672408  PCNA; proliferating cell nuclear antigen [KO:K04802]
101674546  SFN; 14-3-3 protein sigma [KO:K06644]
101685590  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101690611  CHEK2; serine/threonine-protein kinase Chk2 isoform X2 [KO:K06641] [EC:2.7.11.1]
101680806  CDC25A; M-phase inducer phosphatase 1 [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
mpuf03030  DNA replication
mpuf04010  MAPK signaling pathway
mpuf04120  Ubiquitin mediated proteolysis
mpuf04210  Apoptosis
KO pathway
ko04110   
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