KEGG   PATHWAY: ecb04218
Entry
ecb04218                    Pathway                                
Name
Cellular senescence - Equus caballus (horse)
Description
Cellular senescence is a state of irreversible cellular arrest and can be triggered by a number of factors, such as telomere shortening, oncogene activation, irradiation, DNA damage and oxidative stress. It is characterized by enlarged flattened morphology, senescence-associated beta-galactosidase (SA-b-gal) activity, secretion of inflammatory cytokines, growth factors and matrix metalloproteinases, as part of the senescence-associated secretory phenotype (SASP). Cellular senescence is functionally associated with many biological processes including aging, tumor suppression, placental biology, embryonic development, and wound healing.
Class
Cellular Processes; Cell growth and death
Pathway map
ecb04218  Cellular senescence
ecb04218

Other DBs
GO: 0090398
Organism
Equus caballus (horse) [GN:ecb]
Gene
100033843  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100033845  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100033860  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100033900  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
100033931  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
100034117  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100034122  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100034155  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
100034196  IL6; interleukin-6 precursor [KO:K05405]
100034210  EQMHCB2; MHC class I heavy chain precursor [KO:K06751]
100034211  EQMHCC1; MHC class I heavy chain precursor [KO:K06751]
100034212  MHCB3; MHC class I heavy chain precursor [KO:K06751]
100037400  CXCL8; interleukin-8 precursor [KO:K10030]
100049798  [KO:K06751]
100050036  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
100050093  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100050227  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100050377  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100050473  [KO:K06751]
100050481  FOXO1; forkhead box protein O1 [KO:K07201]
100050550  EQMCE1; MHC class I antigen 3.7 precursor [KO:K06751]
100050706  [KO:K06751]
100050762  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
100050775  FOXM1; forkhead box protein M1 isoform X4 [KO:K09406]
100050909  LIN52; protein lin-52 homolog isoform X3 [KO:K21775]
100050939  NBN; nibrin isoform X1 [KO:K10867]
100051000  RASSF5; ras association domain-containing protein 5 isoform X2 [KO:K08015]
100051005  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100051106  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
100051110  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100051150  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100051186  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100051341  MTOR; serine/threonine-protein kinase mTOR isoform X3 [KO:K07203] [EC:2.7.11.1]
100051603  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
100051623  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100051657  [KO:K06751]
100051753  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100051765  TGFB3; transforming growth factor beta-3 [KO:K13377]
100051785  [KO:K07827]
100051790  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
100052084  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100052122  [KO:K02649]
100052135  LIN54; protein lin-54 homolog isoform X3 [KO:K21776]
100052248  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100052657  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X4 [KO:K17332]
100052798  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
100052808  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100053019  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100053056  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
100053119  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
100053481  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
100053856  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
100053882  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100053918  [KO:K06751]
100053946  RAD1; cell cycle checkpoint protein RAD1 isoform X1 [KO:K02830] [EC:3.1.11.2]
100054114  [KO:K06751]
100054213  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
100054397  [KO:K06751]
100054413  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
100054448  [KO:K06751]
100054961  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100054996  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100055184  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100055302  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100055481  HRAS; GTPase HRas isoform X1 [KO:K02833]
100055510  MAPKAPK2; LOW QUALITY PROTEIN: MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100055781  RRAS; ras-related protein R-Ras [KO:K07829]
100056062  [KO:K06751]
100056099  [KO:K06751]
100056139  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
100056182  [KO:K06751]
100056231  [KO:K06751]
100056239  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100056278  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
100056309  [KO:K06751]
100056391  MHCX1; MHC class I antigen 3.5 precursor [KO:K06751]
100057080  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
100057133  CALML5; calmodulin-like protein 5 [KO:K02183]
100057357  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100057483  RELA; transcription factor p65 [KO:K04735]
100057701  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100057866  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
100057875  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100057920  [KO:K06751]
100058141  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100058160  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100058310  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
100059103  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
100059194  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
100059233  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100059288  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
100059354  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
100059469  NRAS; GTPase NRas [KO:K07828]
100059768  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100059994  [KO:K06751]
100060096  [KO:K06751]
100060431  RBL2; retinoblastoma-like protein 2 isoform X2 [KO:K16332]
100060936  MRE11; double-strand break repair protein MRE11 isoform X2 [KO:K10865]
100061130  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100061625  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
100061765  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100061820  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
100061874  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100062044  TP53; cellular tumor antigen p53 [KO:K04451]
100062388  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100062529  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
100062752  CALM1; calmodulin-1 [KO:K02183]
100062974  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
100063155  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
100063190  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100063198  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
100063532  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100063597  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
100064022  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100064223  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
100064276  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
100064353  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100064440  RHEB; GTP-binding protein Rheb [KO:K07208]
100064473  KRAS; GTPase KRas isoform X1 [KO:K07827]
100064482  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
100064557  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100064559  ETS1; protein C-ets-1 isoform X2 [KO:K02678]
100064671  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100064748  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
100064781  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
100064969  IL1A; interleukin-1 alpha precursor [KO:K04383]
100065126  GATA4; transcription factor GATA-4 isoform X4 [KO:K09183]
100065378  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
100065679  TSC2; tuberin isoform X2 [KO:K07207]
100065996  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100066083  HUS1; checkpoint protein HUS1 isoform X3 [KO:K10903]
100066173  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100066552  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
100066558  FOXO3; forkhead box protein O3 [KO:K09408]
100066590  CCND3; G1/S-specific cyclin-D3 isoform X3 [KO:K10152]
100066615  TSC1; hamartin isoform X1 [KO:K07206]
100066812  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
100067231  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
100067434  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100067894  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X4 [KO:K02580]
100068062  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
100068097  MYC; myc proto-oncogene protein [KO:K04377]
100069189  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
100069192  E2F1; transcription factor E2F1 [KO:K17454]
100069786  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100069972  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
100070175  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
100070200  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
100070422  [KO:K02183]
100070694  MYBL2; myb-related protein B [KO:K21769]
100071067  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100071150  CALM3; calmodulin-3 [KO:K02183]
100071586  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
100071908  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
100072219  CCNA2; cyclin-A2 [KO:K06627]
100072299  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100072571  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X2 [KO:K11411] [EC:2.3.1.286]
100072824  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
100072862  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100146128  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
100146270  [KO:K06621]
100146348  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100147188  CCNA1; cyclin-A1 [KO:K06627]
100147205  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
100629145  CALM2; calmodulin-2 [KO:K02183]
100630299  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102147500  [KO:K04443] [EC:2.7.11.1]
102148270  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102149114  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102149157  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
106781398  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
106782258  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111771316  [KO:K13376]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07909  Sirolimus
C16844  Hydroxyl radical
Reference
PMID:24954210
  Authors
Munoz-Espin D, Serrano M
  Title
Cellular senescence: from physiology to pathology.
  Journal
Nat Rev Mol Cell Biol 15:482-96 (2014)
DOI:10.1038/nrm3823
Reference
PMID:26646499
  Authors
Childs BG, Durik M, Baker DJ, van Deursen JM
  Title
Cellular senescence in aging and age-related disease: from mechanisms to therapy.
  Journal
Nat Med 21:1424-35 (2015)
DOI:10.1038/nm.4000
Reference
PMID:26105537
  Authors
Sharpless NE, Sherr CJ
  Title
Forging a signature of in vivo senescence.
  Journal
Nat Rev Cancer 15:397-408 (2015)
DOI:10.1038/nrc3960
Reference
PMID:26435346
  Authors
Fridlyanskaya I, Alekseenko L, Nikolsky N
  Title
Senescence as a general cellular response to stress: A mini-review.
  Journal
Exp Gerontol 72:124-8 (2015)
DOI:10.1016/j.exger.2015.09.021
Reference
PMID:27417123
  Authors
Lujambio A
  Title
To clear, or not to clear (senescent cells)? That is the question.
  Journal
Bioessays 38 Suppl 1:S56-64 (2016)
DOI:10.1002/bies.201670910
Reference
PMID:26564316
  Authors
Di Mitri D, Alimonti A
  Title
Non-Cell-Autonomous Regulation of Cellular Senescence in Cancer.
  Journal
Trends Cell Biol 26:215-26 (2016)
DOI:10.1016/j.tcb.2015.10.005
Reference
PMID:27574725
  Authors
Francica P, Aebersold DM, Medova M
  Title
Senescence as biologic endpoint following pharmacological targeting of receptor tyrosine kinases in cancer.
  Journal
Biochem Pharmacol 126:1-12 (2017)
DOI:10.1016/j.bcp.2016.08.022
Reference
PMID:23982440
  Authors
Bartling B
  Title
Cellular senescence in normal and premature lung aging.
  Journal
Z Gerontol Geriatr 46:613-22 (2013)
DOI:10.1007/s00391-013-0543-3
Reference
PMID:24238962
  Authors
Munoz-Espin D, Canamero M, Maraver A, Gomez-Lopez G, Contreras J, Murillo-Cuesta S, Rodriguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M, Serrano M
  Title
Programmed cell senescence during mammalian embryonic development.
  Journal
Cell 155:1104-18 (2013)
DOI:10.1016/j.cell.2013.10.019
Reference
PMID:26697828
  Authors
Herranz N, Gallage S, Gil J
  Title
TORn about SASP regulation.
  Journal
Cell Cycle 14:3771-2 (2015)
DOI:10.1080/15384101.2015.1105694
Reference
PMID:28410770
  Authors
Martin N, Bernard D
  Title
Calcium signaling and cellular senescence.
  Journal
Cell Calcium S0143-4160(17)30049-0 (2017)
DOI:10.1016/j.ceca.2017.04.001
Reference
PMID:25764980
  Authors
Farfariello V, Iamshanova O, Germain E, Fliniaux I, Prevarskaya N
  Title
Calcium homeostasis in cancer: A focus on senescence.
  Journal
Biochim Biophys Acta 1853:1974-9 (2015)
DOI:10.1016/j.bbamcr.2015.03.005
Reference
PMID:24062309
  Authors
McCarthy DA, Clark RR, Bartling TR, Trebak M, Melendez JA
  Title
Redox control of the senescence regulator interleukin-1alpha and the secretory phenotype.
  Journal
J Biol Chem 288:32149-59 (2013)
DOI:10.1074/jbc.M113.493841
Reference
PMID:27288568
  Authors
Donninger H, Schmidt ML, Mezzanotte J, Barnoud T, Clark GJ
  Title
Ras signaling through RASSF proteins.
  Journal
Semin Cell Dev Biol 58:86-95 (2016)
DOI:10.1016/j.semcdb.2016.06.007
Reference
PMID:28455242
  Authors
Barnoud T, Schmidt ML, Donninger H, Clark GJ
  Title
The role of the NORE1A tumor suppressor in Oncogene-Induced Senescence.
  Journal
Cancer Lett 400:30-36 (2017)
DOI:10.1016/j.canlet.2017.04.030
Reference
PMID:26404840
  Authors
Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ
  Title
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
  Journal
Science 349:aaa5612 (2015)
DOI:10.1126/science.aaa5612
Reference
PMID:26777575
  Authors
Cao X, Li M
  Title
A New Pathway for Senescence Regulation.
  Journal
Genomics Proteomics Bioinformatics 13:333-5 (2015)
DOI:10.1016/j.gpb.2015.11.002
Reference
PMID:25564883
  Authors
Gire V, Dulic V
  Title
Senescence from G2 arrest, revisited.
  Journal
Cell Cycle 14:297-304 (2015)
DOI:10.1080/15384101.2014.1000134
Reference
PMID:24981831
  Authors
Mowla SN, Lam EW, Jat PS
  Title
Cellular senescence and aging: the role of B-MYB.
  Journal
Aging Cell 13:773-9 (2014)
DOI:10.1111/acel.12242
Reference
PMID:22546858
  Authors
Yao H, Chung S, Hwang JW, Rajendrasozhan S, Sundar IK, Dean DA, McBurney MW, Guarente L, Gu W, Ronty M, Kinnula VL, Rahman I
  Title
SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.
  Journal
J Clin Invest 122:2032-45 (2012)
DOI:10.1172/JCI60132
Reference
PMID:23542362
  Authors
Hwang JW, Yao H, Caito S, Sundar IK, Rahman I
  Title
Redox regulation of SIRT1 in inflammation and cellular senescence.
  Journal
Free Radic Biol Med 61:95-110 (2013)
DOI:10.1016/j.freeradbiomed.2013.03.015
Related
pathway
ecb04020  Calcium signaling pathway
ecb04068  FoxO signaling pathway
ecb04110  Cell cycle
ecb04115  p53 signaling pathway
ecb04150  mTOR signaling pathway
KO pathway
ko04218   

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