KEGG   PATHWAY: aamp04110
Entry
aamp04110                   Pathway                                
Name
Cell cycle - Arvicola amphibius (Eurasian water vole)
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
aamp04110  Cell cycle
aamp04110

Other DBs
GO: 0000278
Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119800094  Rb1; retinoblastoma-associated protein [KO:K06618]
119800319  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
119800858  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
119801294  Cdca5; sororin [KO:K17390]
119801903  E2f4; transcription factor E2F4 [KO:K04682]
119801912  Cdt1; DNA replication factor Cdt1 [KO:K10727]
119801993  Orc6; origin recognition complex subunit 6 [KO:K02608]
119802020  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
119802065  Anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
119802072  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
119802601  Fzr1; fizzy-related protein homolog [KO:K03364]
119803023  Ticrr; treslin [KO:K26117]
119803317  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
119803337  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
119803498  Wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
119803501  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
119803891  Orc2; origin recognition complex subunit 2 [KO:K02604]
119803897  Dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
119803901  Orc5; origin recognition complex subunit 5 [KO:K02607]
119803954  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
119804174  [KO:K06626]
119804234  [KO:K16197]
119804610  Stag2; cohesin subunit SA-2 isoform X1 [KO:K06671]
119804620  Smc1a; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
119804622  Bub3; mitotic checkpoint protein BUB3 [KO:K02180]
119804626  Atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
119804628  Ywhah; 14-3-3 protein eta [KO:K16198]
119804938  [KO:K06632] [EC:2.7.11.1]
119804979  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
119805094  Hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
119805267  [KO:K05868]
119805439  [KO:K03875]
119805441  [KO:K03875]
119805442  [KO:K03875]
119806685  Cul1; cullin-1 [KO:K03347]
119806890  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
119807071  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119807407  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
119807493  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
119807661  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
119807764  [KO:K02210] [EC:5.6.2.3]
119807882  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
119808187  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
119808297  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
119808319  Ywhaq; 14-3-3 protein theta [KO:K16197]
119808988  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
119809052  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
119809137  Atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
119809234  Ccnh; LOW QUALITY PROTEIN: cyclin-H [KO:K06634]
119809248  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
119809532  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
119809590  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
119809605  Stag1; cohesin subunit SA-1 isoform X1 [KO:K06671]
119809693  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
119809701  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
119809842  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
119809845  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
119809872  Cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
119810118  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
119810133  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
119810208  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
119810462  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
119810533  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
119810674  Ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
119811275  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
119811297  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
119811558  [KO:K04498] [EC:2.3.1.48]
119811880  Cdc16; LOW QUALITY PROTEIN: cell division cycle protein 16 homolog [KO:K03353]
119812166  Pttg1; securin [KO:K06635]
119812170  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119812234  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
119812278  Pkmyt1; LOW QUALITY PROTEIN: membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
119812405  Ywhae; 14-3-3 protein epsilon [KO:K06630]
119812614  Pds5a; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
119812619  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
119812739  Cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
119812769  Skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
119812917  Cdc6; cell division control protein 6 homolog [KO:K02213]
119812942  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
119813419  Tp53; cellular tumor antigen p53 [KO:K04451]
119814058  Anapc1; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 1 [KO:K03348]
119814141  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
119814342  Esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
119814560  Pcna; proliferating cell nuclear antigen [KO:K04802]
119814594  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
119814613  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
119814778  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
119814812  Cdc25c; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
119814845  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
119814948  Knl1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
119815003  Ywhab; LOW QUALITY PROTEIN: 14-3-3 protein beta/alpha [KO:K16197]
119815108  Cdc23; cell division cycle protein 23 homolog [KO:K03355]
119815142  E2f1; transcription factor E2F1 [KO:K17454]
119815249  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
119815611  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
119816176  Cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
119816383  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
119816691  E2f2; transcription factor E2F2 [KO:K09389]
119816884  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
119816942  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
119817243  Orc1; origin recognition complex subunit 1 [KO:K02603]
119817338  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
119817430  [KO:K04685]
119817507  Sfn; 14-3-3 protein sigma [KO:K06644]
119817628  [KO:K06621]
119817711  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
119817725  Zbtb17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
119817846  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
119817951  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
119818381  Orc4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
119818479  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
119818608  [KO:K04451]
119818860  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
119818916  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
119819022  [KO:K02537]
119819138  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
119819484  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
119820564  [KO:K03094]
119820706  [KO:K06067] [EC:3.5.1.98]
119820755  [KO:K06067] [EC:3.5.1.98]
119820797  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
119820863  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
119820977  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
119821188  Fbxo5; F-box only protein 5 [KO:K10292]
119821456  Tgfb1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
119821457  Ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
119822257  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
119822349  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
119822412  Cdkn1c; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
119822580  Anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
119822767  Anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
119822827  Espl1; LOW QUALITY PROTEIN: separin [KO:K02365] [EC:3.4.22.49]
119822859  [KO:K26093]
119822906  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
119822927  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119822940  Myc; myc proto-oncogene protein [KO:K04377]
119823049  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119823258  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
119823261  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
119823278  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
119823380  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
119823405  [KO:K26116]
119823435  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
119823436  Sgo1; shugoshin 1 [KO:K11580]
119823710  [KO:K06627]
119823829  Smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
119824016  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
119824224  Gsk3b; LOW QUALITY PROTEIN: glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
119824631  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
119824711  Anapc5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
119824783  Prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
119824946  Mad1l1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
119825027  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
119825045  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
119825060  Cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
119825090  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
119825118  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
119825203  Pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
119825607  Ywhag; 14-3-3 protein gamma [KO:K16198]
119826142  Orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
119826163  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
119826292  [KO:K16197]
119826327  E2f5; transcription factor E2F5 [KO:K04682]
119826737  Ccna2; cyclin-A2 [KO:K06627]
119826760  Ccna1; cyclin-A1 [KO:K06627]
119827044  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
119827231  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
119827335  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
119827432  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
119827435  Cdc7; LOW QUALITY PROTEIN: cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
119827524  Mcm6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
121676984  [KO:K17390]
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.
  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
aamp03030  DNA replication
aamp04010  MAPK signaling pathway
aamp04120  Ubiquitin mediated proteolysis
aamp04210  Apoptosis
KO pathway
ko04110   

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