KEGG   PATHWAY: etf04218
Entry
etf04218                    Pathway                                
Name
Cellular senescence - Echinops telfairi (small Madagascar hedgehog)
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
etf04218  Cellular senescence
etf04218

Other DBs
GO: 0090398
Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101650988  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
101639819  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
101642513  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101652427  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
101660774  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
101642964  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105979476  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
101653356  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101654378  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101645619  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101657154  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101657079  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101639447  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
101646101  RB1; retinoblastoma-associated protein isoform X5 [KO:K06618]
101644403  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101658150  RBL2; retinoblastoma-like protein 2 [KO:K16332]
101660509  E2F1; transcription factor E2F1 [KO:K17454]
101661819  E2F2; transcription factor E2F2 [KO:K09389]
101646404  E2F3; transcription factor E2F3 [KO:K06620]
101640899  E2F4; transcription factor E2F4 isoform X3 [KO:K04682]
101641853  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101654217  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101640675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101655654  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101659995  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101657368  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101661221  FOXO1; forkhead box protein O1 [KO:K07201]
101659823  FOXO3; forkhead box protein O3 [KO:K09408]
101660587  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101642843  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
101651720  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101649401  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
105979518  LOW QUALITY PROTEIN: patr class I histocompatibility antigen, B-2 alpha chain-like [KO:K06751]
101659346  class I histocompatibility antigen, Gogo-C*0203 alpha chain isoform X1 [KO:K06751]
101648901  HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751]
101651706  HLA class I histocompatibility antigen, B alpha chain-like isoform X2 [KO:K06751]
101651748  patr class I histocompatibility antigen, A-2 alpha chain-like isoform X2 [KO:K06751]
101656976  HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751]
101639926  KRAS; GTPase KRas isoform X3 [KO:K07827]
101649328  GTPase NRas-like [KO:K07828]
101653520  NRAS; GTPase NRas [KO:K07828]
101657858  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
101655065  MRAS; ras-related protein M-Ras [KO:K07831]
101663997  HRAS; GTPase HRas isoform X1 [KO:K02833]
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101654757  TSC1; hamartin isoform X2 [KO:K07206]
101663717  TSC2; tuberin isoform X1 [KO:K07207]
101648247  RHEB; GTP-binding protein Rheb [KO:K07208]
101664135  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
101655735  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
101657266  CCNA1; cyclin-A1 [KO:K06627]
101642639  CCNA2; cyclin-A2 [KO:K06627]
101646313  MYBL2; myb-related protein B [KO:K21769]
101653744  LIN9; protein lin-9 homolog [KO:K21773]
101659265  LIN37; protein lin-37 homolog isoform X3 [KO:K21774]
101638118  LIN52; protein lin-52 homolog [KO:K21775]
101651761  LIN54; protein lin-54 homolog [KO:K21776]
101658243  LOW QUALITY PROTEIN: histone-binding protein RBBP4-like [KO:K10752]
101657915  LOW QUALITY PROTEIN: histone-binding protein RBBP4-like [KO:K10752]
101663826  RBBP4; histone-binding protein RBBP4 [KO:K10752]
101662792  FOXM1; forkhead box protein M1 isoform X2 [KO:K09406]
101649029  MYC; myc proto-oncogene protein isoform X3 [KO:K04377]
123521593  cyclin-dependent kinase 4 inhibitor B-like [KO:K06621]
101658440  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101647784  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
101656530  TP53; cellular tumor antigen p53 [KO:K04451]
101649790  RASSF5; ras association domain-containing protein 5 [KO:K08015]
101644874  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
101660400  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
101644701  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
101660823  HIPK2; homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
101655821  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
101651680  HIPK3; homeodomain-interacting protein kinase 3 isoform X2 [KO:K08826] [EC:2.7.11.1]
101653184  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101663948  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
101656573  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
101638709  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101656360  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101650474  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101643986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101661568  ETS1; protein C-ets-1 isoform X2 [KO:K02678]
101639675  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
101643832  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
101657745  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101656204  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101653430  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101653940  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101650390  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101660000  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101641486  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101649161  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101659025  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1-like [KO:K05868]
101654399  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101641440  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101664346  MRE11; double-strand break repair protein MRE11 [KO:K10865]
101660609  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
101659249  NBN; LOW QUALITY PROTEIN: nibrin [KO:K10867]
101649302  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101654360  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
101652233  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
101658692  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
101664392  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
101662073  checkpoint protein HUS1-like [KO:K10903]
101638081  HUS1; checkpoint protein HUS1 [KO:K10903]
101647559  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
101640005  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101640269  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101655693  SQSTM1; sequestosome-1 isoform X2 [KO:K14381]
101642683  GATA4; transcription factor GATA-4 isoform X2 [KO:K09183]
101664011  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
101662652  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101663870  RELA; transcription factor p65 [KO:K04735]
101638698  IL1A; interleukin-1 alpha [KO:K04383]
123522712  interleukin-6-like [KO:K05405]
101644240  IL6; interleukin-6 [KO:K05405]
101664548  CXCL8; interleukin-8 [KO:K10030]
101660698  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
101651774  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
101645648  eukaryotic translation initiation factor 4E-binding protein 1-like [KO:K07205]
101651127  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101650104  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
101652039  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
101651425  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101638929  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
101660894  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
101659155  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101648937  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
115871000  calmodulin-A-like [KO:K02183]
101651650  neo-calmodulin-like [KO:K02183]
101662569  CALML6; calmodulin-like protein 6 [KO:K02183]
101656820  CALM3; calmodulin-3 [KO:K02183]
101638094  calmodulin-alpha-like [KO:K02183]
101650375  CALML3; calmodulin-like protein 3 [KO:K02183]
101662916  CALML5; calmodulin-like protein 5 [KO:K02183]
101654870  CALM1; calmodulin-1 [KO:K02183]
101649322  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101643468  CALM2; calmodulin-2 [KO:K02183]
101639952  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
101642124  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101638696  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101660901  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101647023  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101641174  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101639478  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
101664022  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
101645262  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
101654141  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101638553  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101657031  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101638395  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
101643848  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
101648707  ADP/ATP translocase 2 [KO:K05863]
101655091  ADP/ATP translocase 3 [KO:K05863]
101646088  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
101653289  LOW QUALITY PROTEIN: ADP/ATP translocase 2-like [KO:K05863]
101649341  ADP/ATP translocase 2-like [KO:K05863]
101650982  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
101656727  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101653907  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
101649902  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
101642569  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
101640880  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
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
etf04020  Calcium signaling pathway
etf04068  FoxO signaling pathway
etf04110  Cell cycle
etf04115  p53 signaling pathway
etf04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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