KEGG   PATHWAY: tod04110
Entry
tod04110                    Pathway                                
Name
Cell cycle - Talpa occidentalis (Iberian mole)
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
tod04110  Cell cycle
tod04110

Other DBs
GO: 0000278
Organism
Talpa occidentalis (Iberian mole) [GN:tod]
Gene
119230627  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
119230677  TP53; cellular tumor antigen p53 [KO:K04451]
119230688  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
119231601  DBF4B; LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
119231947  [KO:K04685]
119231948  [KO:K06621]
119231965  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
119232026  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
119232098  CDC6; cell division control protein 6 homolog [KO:K02213]
119232154  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
119232261  [KO:K04685]
119232353  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
119232778  CDC14B; dual specificity protein phosphatase CDC14B isoform X4 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
119232790  PCNA; proliferating cell nuclear antigen [KO:K04802]
119232942  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
119232973  YWHAE; 14-3-3 protein epsilon [KO:K06630]
119233018  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
119233407  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
119233685  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
119233838  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
119234016  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
119234468  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
119234529  CDC45; cell division control protein 45 homolog [KO:K06628]
119234545  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
119234735  [KO:K16197]
119234789  CCNA2; cyclin-A2 [KO:K06627]
119234873  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
119234883  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
119234927  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
119235118  ORC1; origin recognition complex subunit 1 [KO:K02603]
119235154  CDC20; cell division cycle protein 20 homolog [KO:K03363]
119235253  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
119235270  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
119235315  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
119235422  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
119235624  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
119235730  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
119236196  SFN; 14-3-3 protein sigma [KO:K06644]
119236323  PTTG1; securin isoform X1 [KO:K06635]
119236368  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
119236726  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
119236881  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
119237269  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
119238040  MYC; LOW QUALITY PROTEIN: myc proto-oncogene protein [KO:K04377]
119238475  MTBP; mdm2-binding protein isoform X3 [KO:K26116]
119238482  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
119238489  KNL1; kinetochore scaffold 1 isoform X1 [KO:K11542]
119238623  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
119238676  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
119238731  [KO:K04802]
119238777  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
119238993  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
119239170  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
119239348  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
119239382  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
119239439  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
119239992  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
119240251  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
119240543  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
119240559  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
119240660  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
119240818  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
119240886  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
119241155  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
119241425  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
119241487  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
119241502  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
119241537  YWHAG; 14-3-3 protein gamma [KO:K16198]
119241606  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
119241821  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
119241984  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
119242005  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
119242143  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
119243034  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
119243064  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
119243150  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
119243161  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
119243428  CDC25C; M-phase inducer phosphatase 3 isoform X3 [KO:K05867] [EC:3.1.3.48]
119243431  CDC23; cell division cycle protein 23 homolog [KO:K03355]
119243468  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119243470  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
119243594  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A isoform X1 [KO:K02537]
119244288  TICRR; treslin [KO:K26117]
119244625  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
119244807  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
119244870  YWHAH; 14-3-3 protein eta [KO:K16198]
119245002  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
119245012  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
119245054  ORC5; origin recognition complex subunit 5 [KO:K02607]
119245606  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
119245623  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
119245917  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
119246141  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
119246152  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
119246910  [KO:K04503]
119247158  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
119247225  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119247226  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
119247311  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
119247528  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
119247697  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119247816  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
119247833  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
119247861  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
119247985  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
119248037  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
119248102  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
119248636  [KO:K13375]
119248858  CUL1; cullin-1 [KO:K03347]
119248895  RBL2; retinoblastoma-like protein 2 [KO:K16332]
119248936  E2F4; transcription factor E2F4 [KO:K04682]
119249185  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
119249194  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
119249350  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
119249625  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
119249863  CDKN1C; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1C [KO:K09993]
119249876  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
119249996  CDCA5; sororin isoform X2 [KO:K17390]
119250005  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
119250289  CDT1; LOW QUALITY PROTEIN: DNA replication factor Cdt1 [KO:K10727]
119250987  [KO:K02087] [EC:2.7.11.22 2.7.11.23]
119251678  E2F3; transcription factor E2F3 [KO:K06620]
119252397  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119252455  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
119252478  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
119252506  MAD2L1BP; MAD2L1-binding protein isoform X3 [KO:K26093]
119252555  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
119252644  TTK; dual specificity protein kinase TTK isoform X2 [KO:K08866] [EC:2.7.12.1]
119252679  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
119252801  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
119253011  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
119253287  [KO:K21770]
119255461  WEE1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
119255597  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
119255790  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
119255810  ORC4; origin recognition complex subunit 4 [KO:K02606]
119256092  ORC2; origin recognition complex subunit 2 [KO:K02604]
119256328  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
119256537  [KO:K17390]
119257218  SGO1; shugoshin 1 [KO:K11580]
119257489  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119257701  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
119257707  TFDP2; transcription factor Dp-2 isoform X3 [KO:K09392]
119257739  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
119257751  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
119257786  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
119258018  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
119258828  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X4 [KO:K11267]
119258844  CCNA1; cyclin-A1 [KO:K06627]
119258908  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
119259200  ANAPC1; anaphase-promoting complex subunit 1 isoform X3 [KO:K03348]
119259204  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
119259478  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
119259564  YWHAQ; 14-3-3 protein theta [KO:K16197]
119259692  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
119259703  TFDP1; transcription factor Dp-1 [KO:K04683]
119260202  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
119260289  NIPBL; nipped-B-like protein [KO:K06672]
119260517  CCNH; cyclin-H isoform X1 [KO:K06634]
119260760  TRIP13; pachytene checkpoint protein 2 homolog isoform X2 [KO:K22399]
119260812  CDK7; cyclin-dependent kinase 7 isoform X2 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
119260871  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
119260933  [KO:K05868]
119261219  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
119261442  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
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.
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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.
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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)
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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)
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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
tod03030  DNA replication
tod04010  MAPK signaling pathway
tod04120  Ubiquitin mediated proteolysis
tod04210  Apoptosis
KO pathway
ko04110   

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