KEGG   PATHWAY: pvp04110
Entry
pvp04110                    Pathway                                
Name
Cell cycle - Pteropus vampyrus (large flying fox)
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
pvp04110  Cell cycle
pvp04110

Other DBs
GO: 0000278
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105307128  uncharacterized protein LOC105307128 [KO:K04503]
105293261  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105288434  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
105307393  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
105294446  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
105300023  RB1; retinoblastoma-associated protein [KO:K06618]
105296511  RBL1; retinoblastoma-like protein 1 [KO:K04681]
105292082  RBL2; retinoblastoma-like protein 2 [KO:K16332]
105298669  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
105290575  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105295257  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105304277  E2F1; transcription factor E2F1 [KO:K17454]
105290449  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105293923  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105305708  E2F4; transcription factor E2F4 [KO:K04682]
105302747  E2F5; transcription factor E2F5 [KO:K04682]
105305086  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
105290352  TFDP2; transcription factor Dp-2 isoform X4 [KO:K09392]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105307945  TGFB1; transforming growth factor beta-1 [KO:K13375]
105296163  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105299206  TGFB3; transforming growth factor beta-3 [KO:K13377]
105292640  SMAD2; mothers against decapentaplegic homolog 2 isoform X3 [KO:K04500]
105309746  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
105292297  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105294340  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
105298440  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X4 [KO:K04685]
105311216  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105297173  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
105305605  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
105302792  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105299522  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
105288383  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105308799  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105302600  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105293569  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
105295712  CUL1; cullin-1 isoform X1 [KO:K03347]
105298053  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105307445  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
105293290  CCNA1; cyclin-A1 [KO:K06627]
105302217  CCNA2; cyclin-A2 [KO:K06627]
105307522  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
105299915  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
105298983  ORC1; origin recognition complex subunit 1 [KO:K02603]
105298134  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
105296987  ORC3; origin recognition complex subunit 3 [KO:K02605]
105291713  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
105295495  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
105310321  origin recognition complex subunit 6-like [KO:K02608]
105301196  ORC6; origin recognition complex subunit 6 [KO:K02608]
105302822  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
105304792  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
105309247  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
105288302  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
105288369  MCM6; LOW QUALITY PROTEIN: DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
105310222  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
105296852  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
105305206  TICRR; treslin [KO:K26117]
105292530  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
105289106  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
105294722  DBF4; protein DBF4 homolog A isoform X2 [KO:K06629]
105303475  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
105298804  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
105309333  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
105294273  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
105309963  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
105298511  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
105293614  CDC25C; M-phase inducer phosphatase 3 isoform X2 [KO:K05867] [EC:3.1.3.48]
105298225  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
105302907  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
105291867  YWHAE; 14-3-3 protein epsilon [KO:K06630]
105299698  YWHAG; 14-3-3 protein gamma [KO:K16198]
105308338  YWHAH; 14-3-3 protein eta [KO:K16198]
105301680  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
105291602  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
105303539  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
105303130  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X2 [KO:K06633] [EC:2.7.11.1]
105303929  CCNH; cyclin-H isoform X1 [KO:K06634]
105309336  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
105303965  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
105298601  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
105303447  CDC27; cell division cycle protein 27 homolog isoform X5 [KO:K03350]
105295611  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
105289203  ANAPC5; anaphase-promoting complex subunit 5 isoform X2 [KO:K03352]
105305089  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
105289208  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
105293611  CDC23; cell division cycle protein 23 homolog [KO:K03355]
105291562  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
105307874  anaphase-promoting complex subunit 10-like [KO:K03357]
105298947  LOW QUALITY PROTEIN: anaphase-promoting complex subunit 11 [KO:K03358]
105292626  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
105288252  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
105303659  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
105288830  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
105297086  CDC20; cell division cycle protein 20 homolog [KO:K03363]
105289893  PTTG1; securin isoform X1 [KO:K06635]
105302660  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
105307808  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
105302050  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
105294517  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
105292236  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
105304240  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
105300836  STAG1; cohesin subunit SA-1 [KO:K06671]
105308888  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
105297305  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
105307452  NIPBL; nipped-B-like protein [KO:K06672]
105296561  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
105307757  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
105291519  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
105292282  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
105293306  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
105293869  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
105288912  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
105297873  sororin-like isoform X2 [KO:K17390]
105291248  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
105289436  SGO1; shugoshin 1 isoform X1 [KO:K11580]
105299964  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105293570  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
105306596  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
105295648  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105288460  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
105297866  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105308612  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
105299291  PPP2R5C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
105295010  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105292319  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
105288637  KNL1; kinetochore scaffold 1 [KO:K11542]
105295294  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
105304456  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X2 [KO:K06679]
105299169  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
105294367  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X3 [KO:K13728]
105288626  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
105295681  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
105303971  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
105301316  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
105288484  MAD2L1-binding protein-like [KO:K26093]
105300442  FZR1; fizzy-related protein homolog [KO:K03364]
105293831  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
105297558  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105307827  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105298051  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
105303098  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105309245  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X2 [KO:K06642] [EC:2.7.11.1]
105294975  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
105297463  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
105301329  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105300252  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105300424  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105295887  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105299404  PCNA; proliferating cell nuclear antigen [KO:K04802]
105290500  SFN; 14-3-3 protein sigma [KO:K06644]
105296813  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
105300942  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
105302354  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
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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)
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Reference
PMID:16936746
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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.
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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.
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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
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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
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Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K
  Title
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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EMBO J 18:396-410 (1999)
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Reference
PMID:17018296
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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.
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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.
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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.
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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)
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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
pvp03030  DNA replication
pvp04010  MAPK signaling pathway
pvp04120  Ubiquitin mediated proteolysis
pvp04210  Apoptosis
KO pathway
ko04110   
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