KEGG   PATHWAY: mlk04110
Entry
mlk04110                    Pathway                                
Name
Cell cycle - Mustela lutreola (European 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
mlk04110  Cell cycle
mlk04110

Other DBs
GO: 0000278
Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131807395  YWHAQ; 14-3-3 protein theta [KO:K16197]
131807584  YWHAB; 14-3-3 protein beta/alpha isoform X1 [KO:K16197]
131807713  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
131807833  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
131807969  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
131807994  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
131808017  PCNA; proliferating cell nuclear antigen [KO:K04802]
131809093  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
131809107  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
131809187  CDC20; cell division cycle protein 20 homolog [KO:K03363]
131809198  SFN; 14-3-3 protein sigma [KO:K06644]
131809310  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
131809499  ORC1; origin recognition complex subunit 1 [KO:K02603]
131809566  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
131809711  E2F2; transcription factor E2F2 [KO:K09389]
131809730  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
131809759  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
131809793  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
131810337  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
131810886  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
131810912  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
131811185  CDC45; cell division control protein 45 homolog [KO:K06628]
131811192  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
131811318  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
131811329  YWHAH; 14-3-3 protein eta [KO:K16198]
131811511  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
131811551  [KO:K16197]
131811552  [KO:K16197]
131811553  [KO:K16197]
131811558  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
131811573  [KO:K16197]
131811852  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
131812299  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
131812330  [KO:K17390]
131812460  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
131812650  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
131812651  [KO:K06621]
131812894  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
131813028  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
131813176  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
131813510  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
131813843  RB1; retinoblastoma-associated protein [KO:K06618]
131813995  CCNA1; cyclin-A1 [KO:K06627]
131814040  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
131814085  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
131814406  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
131815027  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
131815106  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
131815156  [KO:K17390]
131815767  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
131815809  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
131816060  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
131816188  DBF4B; LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
131816423  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
131816637  CDC6; cell division control protein 6 homolog [KO:K02213]
131816838  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
131817001  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
131817379  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
131817428  CDT1; DNA replication factor Cdt1 [KO:K10727]
131817479  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
131817492  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
131817494  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
131817900  E2F4; transcription factor E2F4 [KO:K04682]
131818272  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
131818845  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
131819101  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
131819466  YWHAG; 14-3-3 protein gamma [KO:K16198]
131819513  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
131819828  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
131819979  PLK1; serine/threonine-protein kinase PLK1 isoform X1 [KO:K06631] [EC:2.7.11.21]
131820175  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
131820528  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
131821561  [KO:K06671]
131821853  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
131821883  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
131822121  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
131822190  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
131823251  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
131823289  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
131823526  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
131823807  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
131823881  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
131824307  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
131824494  SGO1; shugoshin 1 [KO:K11580]
131824564  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
131824569  [KO:K06635]
131824571  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
131824745  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
131825052  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
131825056  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
131825080  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
131825206  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
131826401  MYC; myc proto-oncogene protein [KO:K04377]
131826452  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
131826474  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
131826540  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
131826589  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
131826646  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
131826853  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
131826854  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
131826964  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
131826990  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
131827052  [KO:K06635]
131827582  ORC2; origin recognition complex subunit 2 [KO:K02604]
131827695  [KO:K03094]
131828525  CCNA2; cyclin-A2 [KO:K06627]
131828624  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
131828747  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
131828850  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
131828931  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
131829273  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
131829332  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
131829369  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
131829905  CUL1; cullin-1 [KO:K03347]
131830219  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
131830582  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
131830701  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
131831532  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
131831657  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
131831665  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
131831861  PTTG1; securin isoform X1 [KO:K06635]
131832040  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
131832090  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
131832093  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
131832262  [KO:K05868]
131832312  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
131832315  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
131832435  CCNH; cyclin-H isoform X1 [KO:K06634]
131832942  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
131833355  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
131833442  FBXO5; F-box only protein 5 [KO:K10292]
131833482  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
131833616  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
131833659  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
131833891  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
131833967  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
131833991  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
131834020  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
131834089  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
131834799  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
131835390  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
131835609  TICRR; treslin isoform X1 [KO:K26117]
131835761  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
131835871  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
131835965  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
131836103  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
131836118  KNL1; kinetochore scaffold 1 [KO:K11542]
131836599  [KO:K02178] [EC:2.7.11.1]
131836664  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
131836852  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
131836998  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
131838215  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
131838387  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
131838412  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
131838541  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
131838622  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
131838700  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
131839026  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
131839136  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
131839402  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
131839520  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
131839523  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
131839608  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
131840443  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
131840449  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
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)
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
mlk03030  DNA replication
mlk04010  MAPK signaling pathway
mlk04120  Ubiquitin mediated proteolysis
mlk04210  Apoptosis
KO pathway
ko04110   

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