KEGG   PATHWAY: nvs04110
Entry
nvs04110                    Pathway                                
Name
Cell cycle - Neogale vison (American mink)
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
nvs04110  Cell cycle
nvs04110

Other DBs
GO: 0000278
Organism
Neogale vison (American mink) [GN:nvs]
Gene
122889157  [KO:K06635]
122889168  CCNA2; cyclin-A2 [KO:K06627]
122889187  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
122889369  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
122889616  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
122889659  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
122889837  [KO:K16197]
122889911  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
122890128  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
122890497  [KO:K05868]
122891038  [KO:K11273] [EC:3.6.4.13]
122891205  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
122891259  CDC23; cell division cycle protein 23 homolog [KO:K03355]
122891326  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
122891390  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
122891468  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
122891583  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
122891679  [KO:K04382] [EC:3.1.3.16]
122891690  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
122891702  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122891785  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122892356  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
122892390  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
122892405  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
122892551  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
122892604  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
122892918  KNL1; kinetochore scaffold 1 isoform X1 [KO:K11542]
122893082  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
122893231  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
122893283  PTTG1; securin isoform X1 [KO:K06635]
122893443  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
122893639  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
122893946  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
122894006  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
122894104  TICRR; treslin isoform X1 [KO:K26117]
122895279  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
122895358  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
122895366  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
122895401  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
122895538  PLK1; serine/threonine-protein kinase PLK1 isoform X1 [KO:K06631] [EC:2.7.11.21]
122895577  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
122895878  [KO:K04498] [EC:2.3.1.48]
122896140  YWHAG; 14-3-3 protein gamma [KO:K16198]
122896292  [KO:K06671]
122896295  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
122896456  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
122896867  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
122897032  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
122897190  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
122897239  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
122898612  E2F2; transcription factor E2F2 [KO:K09389]
122899454  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
122899487  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
122899618  SFN; 14-3-3 protein sigma [KO:K06644]
122899699  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
122899857  CDC20; cell division cycle protein 20 homolog isoform X1 [KO:K03363]
122899958  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
122899973  ORC1; origin recognition complex subunit 1 [KO:K02603]
122900071  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122900187  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
122900244  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122900565  [KO:K03094]
122900702  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
122900775  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
122900855  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
122901107  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
122901191  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
122901954  [KO:K03094]
122902183  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
122902420  [KO:K03868] [EC:2.3.2.32]
122902673  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
122902700  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
122902875  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
122902898  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
122902993  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
122903004  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
122903164  CDC45; cell division control protein 45 homolog [KO:K06628]
122903173  FBXO5; F-box only protein 5 [KO:K10292]
122903233  YWHAH; 14-3-3 protein eta [KO:K16198]
122903292  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
122903407  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
122903442  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
122903451  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
122904134  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
122904298  MYC; myc proto-oncogene protein [KO:K04377]
122904336  [KO:K26116]
122904354  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
122904378  [KO:K03094]
122904393  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
122904429  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
122904477  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
122904612  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
122904613  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
122904731  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
122904780  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
122904783  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
122904813  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122905139  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
122905176  CUL1; cullin-1 [KO:K03347]
122905882  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
122906102  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
122906134  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
122906283  CDC6; cell division control protein 6 homolog [KO:K02213]
122906357  YWHAE; 14-3-3 protein epsilon [KO:K06630]
122906719  TP53; cellular tumor antigen p53 [KO:K04451]
122906737  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
122907010  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
122907082  RB1; retinoblastoma-associated protein [KO:K06618]
122907266  TFDP1; transcription factor Dp-1 [KO:K04683]
122907270  CDC16; cell division cycle protein 16 homolog [KO:K03353]
122907321  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122907830  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
122908116  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
122908357  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
122908538  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
122908557  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
122908562  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
122908608  [KO:K26093]
122908918  STAG1; cohesin subunit SA-1 [KO:K06671]
122908925  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
122909017  SGO1; shugoshin 1 [KO:K11580]
122909094  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
122909136  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
122909467  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
122909521  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
122909889  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
122909911  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122910770  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
122911135  CDT1; DNA replication factor Cdt1 [KO:K10727]
122911358  E2F4; transcription factor E2F4 [KO:K04682]
122911451  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
122911484  ORC6; origin recognition complex subunit 6 [KO:K02608]
122911494  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
122911710  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
122912064  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
122912225  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
122912265  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
122912289  [KO:K06067] [EC:3.5.1.98]
122912413  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
122912635  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
122912715  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
122913079  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
122913087  [KO:K17390]
122913122  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
122913270  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
122914595  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
122915095  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
122915103  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
122915324  YWHAQ; 14-3-3 protein theta [KO:K16197]
122916044  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
122916095  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
122916153  E2F1; transcription factor E2F1 [KO:K17454]
122916228  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
122916241  PCNA; proliferating cell nuclear antigen [KO:K04802]
122916724  [KO:K03094]
122916992  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122917065  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
122917157  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
122917335  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
122917340  [KO:K16197]
122917558  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122917624  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122917740  CCNH; cyclin-H isoform X1 [KO:K06634]
122918428  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122918553  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
122918843  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
122918883  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
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)
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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)
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Reference
PMID:12573239
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
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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)
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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
nvs03030  DNA replication
nvs04010  MAPK signaling pathway
nvs04120  Ubiquitin mediated proteolysis
nvs04210  Apoptosis
KO pathway
ko04110   

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