KEGG   PATHWAY: myb04110
Entry
myb04110                    Pathway                                
Name
Cell cycle - Myotis brandtii (Brandt's bat)
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
myb04110  Cell cycle
myb04110

Other DBs
GO: 0000278
Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102263484  CCND1; cyclin D1 [KO:K04503]
102254218  CCND2; cyclin D2 [KO:K10151]
102252389  CCND3; cyclin D3 [KO:K10152]
102261527  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102258140  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102251785  RB1; RB transcriptional corepressor 1 [KO:K06618]
102250026  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102251179  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102255271  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
102242800  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102243153  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102242618  E2F1; E2F transcription factor 1 [KO:K17454]
102256714  E2F2; E2F transcription factor 2 [KO:K09389]
102259711  E2F3; E2F transcription factor 3 [KO:K06620]
102243595  E2F5; E2F transcription factor 5 [KO:K04682]
102246782  E2F4; E2F transcription factor 4 [KO:K04682]
102257240  TFDP1; transcription factor Dp-1 [KO:K04683]
102244338  TFDP2; transcription factor Dp-2 [KO:K09392]
102248758  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102262083  TGFB1; transforming growth factor beta 1 [KO:K13375]
102250887  TGFB2; transforming growth factor beta 2 [KO:K13376]
102249502  TGFB3; transforming growth factor beta 3 [KO:K13377]
102256193  SMAD2; SMAD family member 2 [KO:K04500]
102259468  SMAD3; SMAD family member 3 [KO:K23605]
102259994  SMAD4; SMAD family member 4 [KO:K04501]
102257498  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102251899  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
102260311  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
102260903  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
102257630  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
102241702  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
102252017  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
102245891  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102248984  CCNE2; cyclin E2 [KO:K06626]
102256122  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102251595  SKP1; S-phase kinase associated protein 1 [KO:K03094]
102251629  S-phase kinase-associated protein 1 [KO:K03094]
102245795  CUL1; cullin 1 [KO:K03347]
102243164  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102260998  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
102254932  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102243482  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102262715  SKP2; S-phase kinase associated protein 2 [KO:K03875]
102241823  CCNA1; cyclin A1 [KO:K06627]
102251987  CCNA2; cyclin A2 [KO:K06627]
102261548  CDC6; cell division cycle 6 [KO:K02213]
102244000  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
102249744  ORC1; origin recognition complex subunit 1 [KO:K02603]
102246665  ORC2; origin recognition complex subunit 2 [KO:K02604]
102248274  ORC3; origin recognition complex subunit 3 [KO:K02605]
102254151  ORC4; origin recognition complex subunit 4 [KO:K02606]
102249400  ORC5; origin recognition complex subunit 5 [KO:K02607]
102249280  ORC6; origin recognition complex subunit 6 [KO:K02608]
102251603  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
102251205  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
102245047  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
102249315  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
102244902  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
102244229  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
102254904  CDC45; cell division cycle 45 [KO:K06628]
102240420  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
102248419  MTBP; MDM2 binding protein [KO:K26116]
102244679  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
102244856  DBF4; DBF4 zinc finger [KO:K06629]
102240408  DBF4B; DBF4 zinc finger B [KO:K06629]
102255275  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102243790  CCNB1; cyclin B1 [KO:K05868]
102261943  CCNB2; cyclin B2 [KO:K21770]
102240520  CCNB3; cyclin B3 [KO:K21771]
102244544  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
102262547  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
102246440  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
102261683  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
102261238  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
102256309  14-3-3 protein zeta/delta-like [KO:K16197]
102253232  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102244681  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
102242657  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
102260682  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
102244442  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
102252222  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
102245788  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
102239469  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
102247663  CCNH; cyclin H [KO:K06634]
102244078  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102258943  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
102240993  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
102261522  CDC27; cell division cycle 27 [KO:K03350]
102249169  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
102251439  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
102260655  CDC16; cell division cycle 16 [KO:K03353]
102262204  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
102257472  CDC23; cell division cycle 23 [KO:K03355]
102242432  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
102248022  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
102242651  CDC26; cell division cycle 26 [KO:K03359]
102242126  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
102254780  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
102249055  anaphase-promoting complex subunit 15 [KO:K25228]
102258696  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
102252102  CDC20; cell division cycle 20 [KO:K03363]
102262804  cell division cycle protein 20 homolog [KO:K03363]
102256908  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
102259018  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
102252776  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
102253503  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
102252221  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
102263253  RAD21; RAD21 cohesin complex component [KO:K06670]
102240513  STAG1; stromal antigen 1 [KO:K06671]
102247466  STAG2; stromal antigen 2 [KO:K06671]
102248976  ATRX; ATRX, chromatin remodeler [KO:K10779]
102250719  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
102260025  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
102250140  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
102260131  histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
102241535  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
102243365  histone deacetylase 8-like [KO:K11405] [EC:3.5.1.98]
102250633  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
102251474  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
102256431  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
102258403  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
102255703  WAPL; WAPL cohesin release factor [KO:K25163]
102261359  sororin [KO:K17390]
102251550  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
102240303  SGO1; shugoshin 1 [KO:K11580]
102246010  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102255371  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102262643  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102254517  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102241218  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102242374  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102239026  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102249194  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102244211  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102258715  NDC80; NDC80, kinetochore complex component [KO:K11547]
102256740  KNL1; kinetochore scaffold 1 [KO:K11542]
102255088  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
102262354  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
102261315  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102248892  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
102240772  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102243286  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
102253751  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
102252852  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
102256429  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
102239253  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
102239449  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
102257253  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
102252919  FBXO5; F-box protein 5 [KO:K10292]
102255221  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102256311  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102249541  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102260716  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102244634  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102258109  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102256024  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102244768  TP53; tumor protein p53 [KO:K04451]
102242156  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102246302  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102239140  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102245639  PCNA; proliferating cell nuclear antigen [KO:K04802]
102262200  SFN; stratifin [KO:K06644]
102255905  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102250232  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102252775  M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
102240322  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102252873  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
myb03030  DNA replication
myb04010  MAPK signaling pathway
myb04120  Ubiquitin mediated proteolysis
myb04210  Apoptosis
KO pathway
ko04110   
LinkDB

DBGET integrated database retrieval system