KEGG   PATHWAY: hai04110
Entry
hai04110                    Pathway                                
Name
Cell cycle - Hipposideros armiger (great roundleaf 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
hai04110  Cell cycle
hai04110

Other DBs
GO: 0000278
Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109371173  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
109371356  CDC14A; dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109371552  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
109371683  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
109371901  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109372391  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
109372421  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
109372579  ORC1; origin recognition complex subunit 1 [KO:K02603]
109373194  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
109373248  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
109373579  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
109373596  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
109374090  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109374675  [KO:K06621]
109374676  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
109374770  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
109374881  [KO:K06635]
109375133  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
109375294  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
109375599  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
109375671  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
109375680  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
109375911  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
109376215  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
109376590  TGFB1; transforming growth factor beta-1 [KO:K13375]
109377147  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
109377242  E2F1; transcription factor E2F1 [KO:K17454]
109377484  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109377641  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
109377832  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
109377836  FBXO5; F-box only protein 5 [KO:K10292]
109379146  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
109379199  ORC2; origin recognition complex subunit 2 [KO:K02604]
109379352  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
109379521  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
109379983  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
109380140  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
109380261  CDC27; cell division cycle protein 27 homolog [KO:K03350]
109380620  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
109380669  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
109380808  CDC6; cell division control protein 6 homolog [KO:K02213]
109381056  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
109381205  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109381277  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
109381436  TICRR; treslin [KO:K26117]
109381619  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
109381623  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
109381699  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
109381811  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
109381827  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
109381972  CCNH; cyclin-H [KO:K06634]
109382460  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
109382545  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
109382554  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
109382627  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
109382710  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
109382800  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
109382857  MAD2L1BP; MAD2L1-binding protein isoform X1 [KO:K26093]
109382865  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
109382891  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109382969  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109383036  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
109383046  ORC6; origin recognition complex subunit 6 [KO:K02608]
109383089  YWHAH; 14-3-3 protein eta [KO:K16198]
109383166  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
109383211  MYC; myc proto-oncogene protein [KO:K04377]
109383408  CDC20; cell division cycle protein 20 homolog isoform X1 [KO:K03363]
109383411  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
109383495  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
109383846  PCNA; proliferating cell nuclear antigen [KO:K04802]
109383851  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
109383918  [KO:K03353]
109383949  TFDP1; transcription factor Dp-1 [KO:K04683]
109383975  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
109383978  KNL1; protein CASC5 [KO:K11542]
109384306  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
109384316  CDCA5; sororin isoform X1 [KO:K17390]
109384550  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
109384760  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
109384912  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
109384926  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109385039  YWHAG; 14-3-3 protein gamma [KO:K16198]
109385242  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
109385661  ATRX; transcriptional regulator ATRX [KO:K10779]
109386056  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
109386068  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
109386529  PLK1; serine/threonine-protein kinase PLK1 isoform X1 [KO:K06631] [EC:2.7.11.21]
109386669  YWHAQ; 14-3-3 protein theta [KO:K16197]
109386699  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
109386721  SFN; 14-3-3 protein sigma [KO:K06644]
109386914  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109387061  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
109387065  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
109387138  RB1; retinoblastoma-associated protein [KO:K06618]
109387511  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
109387574  E2F5; transcription factor E2F5 [KO:K04682]
109387640  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
109387806  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
109388212  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
109388396  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109388453  CCNA1; cyclin-A1 [KO:K06627]
109388596  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
109388695  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
109388844  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
109388962  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
109388999  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
109389172  CDT1; DNA replication factor Cdt1 [KO:K10727]
109389238  STAG1; cohesin subunit SA-1 [KO:K06671]
109389245  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
109389297  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
109389399  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
109389524  ORC5; origin recognition complex subunit 5 [KO:K02607]
109389553  RBL1; retinoblastoma-like protein 1 [KO:K04681]
109390037  E2F4; transcription factor E2F4 [KO:K04682]
109390146  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
109390269  CDKN2C; cyclin-dependent kinase 4 inhibitor C isoform X1 [KO:K06622]
109390465  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
109390584  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109390689  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
109390747  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
109390885  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
109391250  MCM2; LOW QUALITY PROTEIN: DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
109391294  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
109391372  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
109391595  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
109391669  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
109391774  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
109392135  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109392220  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
109392262  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
109392275  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109392488  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
109392680  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
109392681  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
109392712  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
109392961  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
109392993  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
109393068  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
109393112  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
109393527  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
109393539  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
109393932  [KO:K03355]
109393982  SGO1; shugoshin 1 [KO:K11580]
109394210  PTTG1; securin isoform X1 [KO:K06635]
109394672  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
109394730  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
109394996  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
109395084  MTBP; mdm2-binding protein [KO:K26116]
109395127  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
109395450  CUL1; cullin-1 isoform X1 [KO:K03347]
109395598  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
109395914  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
109395991  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
109396383  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
109396675  CCNA2; cyclin-A2 [KO:K06627]
109396882  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
109396914  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
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
hai03030  DNA replication
hai04010  MAPK signaling pathway
hai04120  Ubiquitin mediated proteolysis
hai04210  Apoptosis
KO pathway
ko04110   

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