KEGG   PATHWAY: efus04110
Entry
efus04110                   Pathway                                
Name
Cell cycle - Eptesicus fuscus (big brown 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
efus04110  Cell cycle
efus04110

Other DBs
GO: 0000278
Organism
Eptesicus fuscus (big brown bat) [GN:efus]
Gene
103290903  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103288032  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103301919  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
103292479  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
103292850  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
103289677  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
103293313  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103295856  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103296016  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
103300141  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
103303280  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103293384  LOW QUALITY PROTEIN: histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
103293372  E2F1; transcription factor E2F1 [KO:K17454]
103292075  E2F2; transcription factor E2F2 [KO:K09389]
103290149  E2F3; transcription factor E2F3 [KO:K06620]
103284569  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
103303367  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
103288210  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
103299603  TFDP2; transcription factor Dp-2 [KO:K09392]
103290720  GSK3B; glycogen synthase kinase-3 beta isoform X3 [KO:K03083] [EC:2.7.11.26]
103284692  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
103293466  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
103283554  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103283787  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103292171  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
103292358  MYC; myc proto-oncogene protein [KO:K04377]
103292023  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
103297403  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
103297385  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103284032  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
103301126  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
103285100  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
103304073  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
103295571  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103292334  CCNE2; G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
103284864  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
103292405  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
129152067  S-phase kinase-associated protein 1-like [KO:K03094]
129149958  S-phase kinase-associated protein 1 [KO:K03094]
103297252  CUL1; cullin-1 isoform X1 [KO:K03347]
103288833  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
103298086  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
103301644  CCNA2; cyclin-A2 isoform X1 [KO:K06627]
103303305  CCNA1; cyclin-A1 [KO:K06627]
103289018  CDC6; cell division control protein 6 homolog [KO:K02213]
103284751  CDT1; DNA replication factor Cdt1 [KO:K10727]
103284022  ORC1; origin recognition complex subunit 1 [KO:K02603]
103290546  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
103291196  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
103283423  ORC4; origin recognition complex subunit 4 [KO:K02606]
103293495  ORC5; origin recognition complex subunit 5 isoform X4 [KO:K02607]
103295873  ORC6; origin recognition complex subunit 6 [KO:K02608]
103302381  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
103300623  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
103287579  MCM4; DNA replication licensing factor MCM4 isoform X1 [KO:K02212] [EC:5.6.2.3]
103288911  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
103287766  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
103285970  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
103286971  CDC45; cell division control protein 45 homolog [KO:K06628]
103302773  TICRR; treslin [KO:K26117]
103287647  MTBP; mdm2-binding protein [KO:K26116]
103297982  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
103293113  DBF4; protein DBF4 homolog A [KO:K06629]
103293221  DBF4B; protein DBF4 homolog B [KO:K06629]
103289545  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103305163  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103283847  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103301323  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
103285639  CDC25B; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
103289927  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
103292308  YWHAZ; 14-3-3 protein zeta/delta isoform X1 [KO:K16197]
103301717  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103305598  YWHAQ; 14-3-3 protein theta isoform X2 [KO:K16197]
103299031  14-3-3 protein theta-like [KO:K16197]
103291757  YWHAE; 14-3-3 protein epsilon [KO:K06630]
103286022  YWHAG; 14-3-3 protein gamma [KO:K16198]
103287126  YWHAH; 14-3-3 protein eta [KO:K16198]
103296209  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
103294630  WEE1; wee1-like protein kinase isoform X2 [KO:K06632] [EC:2.7.11.1]
103294082  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
103286180  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
103305248  CCNH; cyclin-H isoform X1 [KO:K06634]
103305165  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
103302912  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
103296103  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
103293161  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
103285012  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
103287030  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
103288203  CDC16; cell division cycle protein 16 homolog [KO:K03353]
103287039  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
103289948  CDC23; cell division cycle protein 23 homolog [KO:K03355]
103288144  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
103298226  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
103303921  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
103296403  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
103293565  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
129148615  anaphase-promoting complex subunit 15-like [KO:K25228]
103289483  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
103294824  CDC20; cell division cycle protein 20 homolog [KO:K03363]
103291588  PTTG1; securin isoform X1 [KO:K06635]
103285342  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
103298637  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
103301349  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
103288557  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
103287663  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
103296300  STAG1; cohesin subunit SA-1 [KO:K06671]
103301898  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
103303647  ATRX; transcriptional regulator ATRX [KO:K10779]
103303662  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
103298810  NIPBL; nipped-B-like protein [KO:K06672]
103299509  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
103285834  histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
103300732  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
103303192  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
103294336  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
103284917  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
103304235  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
103292809  WAPL; wings apart-like protein homolog isoform X2 [KO:K25163]
103302068  CDCA5; sororin [KO:K17390]
103296875  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
103296896  SGO1; shugoshin 1 [KO:K11580]
103286718  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
103290347  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
103293769  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103304255  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
103283666  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103290054  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
103296652  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103298034  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
103302063  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
103303033  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
103287510  KNL1; kinetochore scaffold 1 [KO:K11542]
103287641  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
103299163  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
103298145  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
129147519  LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD2A-like [KO:K02537]
103295327  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
103287305  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
103299313  BUB3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
103302913  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
103305310  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
103296630  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
103294247  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
103297950  FBXO5; F-box only protein 5 [KO:K10292]
103297889  CDC14B; dual specificity protein phosphatase CDC14B isoform X5 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103291311  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103286158  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
103288832  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
103287690  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
103301572  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
103292522  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103296897  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
103284106  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
103294264  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103299999  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103285652  PCNA; proliferating cell nuclear antigen [KO:K04802]
103291909  SFN; 14-3-3 protein sigma [KO:K06644]
103286938  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
103287141  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
103300851  CDC25A; M-phase inducer phosphatase 1 isoform X1 [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
efus03030  DNA replication
efus04010  MAPK signaling pathway
efus04120  Ubiquitin mediated proteolysis
efus04210  Apoptosis
KO pathway
ko04110   
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