KEGG   PATHWAY: myd04110
Entry
myd04110                    Pathway                                
Name
Cell cycle - Myotis davidii (David's myotis)
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
myd04110  Cell cycle
myd04110

Other DBs
GO: 0000278
Organism
Myotis davidii (David's myotis) [GN:myd]
Gene
102751662  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102751668  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102751752  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102751983  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102752054  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
102752072  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
102752341  CCNA1; cyclin A1 [KO:K06627]
102752386  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102752485  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
102752810  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
102752858  [KO:K11405] [EC:3.5.1.98]
102752906  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
102752949  SMAD4; SMAD family member 4 [KO:K04501]
102752983  TGFB1; transforming growth factor beta 1 [KO:K13375]
102753214  NDC80; NDC80, kinetochore complex component [KO:K11547]
102753269  [KO:K25228]
102753326  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
102753396  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
102753675  CCNB1; cyclin B1 [KO:K05868]
102753689  [KO:K05866] [EC:3.1.3.48]
102753881  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
102754141  STAG1; stromal antigen 1 [KO:K06671]
102754667  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102754758  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
102754832  SGO1; shugoshin 1 [KO:K11580]
102755202  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
102755290  E2F4; E2F transcription factor 4 [KO:K04682]
102755318  CDC6; cell division cycle 6 [KO:K02213]
102755439  E2F2; E2F transcription factor 2 [KO:K09389]
102755576  CDC45; cell division cycle 45 [KO:K06628]
102755658  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102755701  CCND2; cyclin D2 [KO:K10151]
102755809  STAG2; stromal antigen 2 [KO:K06671]
102755907  [KO:K06644]
102755920  TGFB2; transforming growth factor beta 2 [KO:K13376]
102756465  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
102756495  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
102756513  SKP1; S-phase kinase associated protein 1 [KO:K03094]
102756757  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102756838  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102756852  DBF4; DBF4 zinc finger [KO:K06629]
102756859  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
102756889  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:3.6.4.13]
102756923  CCND3; cyclin D3 [KO:K10152]
102756936  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
102757524  [KO:K03363]
102757649  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
102757714  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
102757729  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
102757913  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102758104  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102758132  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
102758384  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
102758527  KNL1; kinetochore scaffold 1 [KO:K11542]
102758544  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102758648  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102758650  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
102758704  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
102758798  [KO:K11405] [EC:3.5.1.98]
102758819  SMAD2; SMAD family member 2 [KO:K04500]
102758841  CCNA2; cyclin A2 [KO:K06627]
102758898  TFDP2; transcription factor Dp-2 [KO:K09392]
102758995  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102759012  TP53; tumor protein p53 [KO:K04451]
102759026  E2F1; E2F transcription factor 1 [KO:K17454]
102759298  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
102759739  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102759793  CCND1; cyclin D1 [KO:K04503]
102759866  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
102760017  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102760359  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
102760373  CDC27; cell division cycle 27 [KO:K03350]
102760469  TFDP1; transcription factor Dp-1 [KO:K04683]
102760528  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102760761  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102760790  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
102761068  FBXO5; F-box protein 5 [KO:K10292]
102761131  MTBP; MDM2 binding protein [KO:K26116]
102761242  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
102761266  ORC5; origin recognition complex subunit 5 [KO:K02607]
102761506  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
102761562  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102761846  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102761917  CCNB3; cyclin B3 [KO:K21771]
102762106  CDC23; cell division cycle 23 [KO:K03355]
102762133  CCNH; cyclin H [KO:K06634]
102762261  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
102762331  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
102762525  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
102762653  ORC1; origin recognition complex subunit 1 [KO:K02603]
102762679  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102762718  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
102762854  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102763143  E2F5; E2F transcription factor 5 [KO:K04682]
102763310  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
102763547  CCNE2; cyclin E2 [KO:K06626]
102763745  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
102764610  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102764679  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102764841  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
102765197  [KO:K04685]
102765231  CDC16; cell division cycle 16 [KO:K03353]
102765455  ORC2; origin recognition complex subunit 2 [KO:K02604]
102765675  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
102765745  [KO:K16197]
102765886  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
102765893  RAD21; RAD21 cohesin complex component [KO:K06670]
102766057  [KO:K04685]
102766115  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
102766251  RB1; RB transcriptional corepressor 1 [KO:K06618]
102766417  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
102766522  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102766642  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
102767192  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
102767291  TGFB3; transforming growth factor beta 3 [KO:K13377]
102767336  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102767522  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102767684  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
102767740  DBF4B; DBF4 zinc finger B [KO:K06629]
102767838  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102768307  E2F3; E2F transcription factor 3 [KO:K06620]
102768661  CDC26; cell division cycle 26 [KO:K03359]
102768675  [KO:K11267]
102768732  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
102768776  ORC4; origin recognition complex subunit 4 [KO:K02606]
102769157  [KO:K10779]
102769241  SMAD3; SMAD family member 3 [KO:K23605]
102769723  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
102769827  CCNE1; cyclin E1 [KO:K06626]
102770564  SKP2; S-phase kinase associated protein 2 [KO:K03875]
102770567  CDC20; cell division cycle 20 [KO:K03363]
102770674  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
102770810  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
102770816  ATRX; ATRX, chromatin remodeler [KO:K10779]
102770877  WAPL; WAPL cohesin release factor [KO:K25163]
102771035  PCNA; proliferating cell nuclear antigen [KO:K04802]
102771060  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
102771124  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
102771162  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102771406  CUL1; cullin 1 [KO:K03347]
102771581  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102771922  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102772070  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
102772088  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
102772302  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
102772616  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
102772628  ORC3; origin recognition complex subunit 3 [KO:K02605]
102772635  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
102772934  [KO:K06644]
102773038  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102773081  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102773412  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102773489  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
102773677  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
102773702  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
102773716  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102773727  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
102774510  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
102774679  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
102774710  CDCA5; cell division cycle associated 5 [KO:K17390]
102775253  ORC6; origin recognition complex subunit 6 [KO:K02608]
102775345  CCNB2; cyclin B2 [KO:K21770]
102775537  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
107182127  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
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
myd03030  DNA replication
myd04010  MAPK signaling pathway
myd04120  Ubiquitin mediated proteolysis
myd04210  Apoptosis
KO pathway
ko04110   

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