KEGG   PATHWAY: gvr04218
Entry
gvr04218                    Pathway                                
Name
Cellular senescence - Galeopterus variegatus (Sunda flying lemur)
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
gvr04218  Cellular senescence
gvr04218

Other DBs
GO: 0090398
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103582022  TSC1; hamartin [KO:K07206]
103582032  [KO:K06269] [EC:3.1.3.16]
103582204  [KO:K04973]
103583154  [KO:K02216] [EC:2.7.11.1]
103583282  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103585050  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
103585436  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103585463  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103585512  ETS1; protein C-ets-1 [KO:K02678]
103585615  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103585833  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103585928  IL6; interleukin-6 [KO:K05405]
103585960  TGFB3; transforming growth factor beta-3 [KO:K13377]
103585976  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
103586032  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
103586284  LIN52; protein lin-52 homolog [KO:K21775]
103586434  [KO:K06751]
103586572  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103586784  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103586826  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
103586861  E2F1; transcription factor E2F1 [KO:K17454]
103587310  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
103587459  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
103587477  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587478  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587820  MYC; myc proto-oncogene protein [KO:K04377]
103587883  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103588373  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103588449  CALM1; calmodulin [KO:K02183]
103588692  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
103589264  [KO:K15041]
103589291  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
103589329  NRAS; GTPase NRas [KO:K07828]
103589614  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
103589979  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
103589995  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
103590136  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103590142  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
103590184  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
103590253  E2F3; transcription factor E2F3 [KO:K06620]
103590274  MRE11A; double-strand break repair protein MRE11A isoform X1 [KO:K10865]
103590279  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103590291  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
103590618  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103590624  E2F2; transcription factor E2F2 [KO:K09389]
103590777  RASSF5; ras association domain-containing protein 5 [KO:K08015]
103591114  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
103591330  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
103591379  CXCL8; interleukin-8 [KO:K10030]
103591400  TP53; cellular tumor antigen p53 [KO:K04451]
103591559  RHEB; GTP-binding protein Rheb [KO:K07208]
103591612  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
103591905  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
103591910  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
103592005  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
103592192  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103592400  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
103592560  [KO:K06751]
103592599  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103592600  RRAS; ras-related protein R-Ras [KO:K07829]
103592823  LIN37; protein lin-37 homolog [KO:K21774]
103592918  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]
103592983  CALM3; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
103593362  GATA4; transcription factor GATA-4 [KO:K09183]
103593663  RB1; retinoblastoma-associated protein [KO:K06618]
103593683  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103593976  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103594623  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
103594960  RBL2; retinoblastoma-like protein 2 [KO:K16332]
103595293  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
103595334  RELA; transcription factor p65 [KO:K04735]
103595826  IL1A; interleukin-1 alpha [KO:K04383]
103596129  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103596384  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103596897  TRAF3IP2; adapter protein CIKS [KO:K21124]
103596994  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
103597016  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103597025  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
103597242  FOXO3; forkhead box protein O3 [KO:K09408]
103597250  FOXO1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
103597510  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
103597582  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
103597698  [KO:K04960]
103597742  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
103597771  MYBL2; myb-related protein B [KO:K21769]
103597845  TSC2; tuberin isoform X1 [KO:K07207]
103597990  RBBP4; histone-binding protein RBBP4 [KO:K10752]
103598080  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
103598106  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103598210  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103598251  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103598325  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103598392  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
103598453  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103598637  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103598989  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
103599172  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103599185  [KO:K13375]
103599191  [KO:K13375]
103599501  KRAS; GTPase KRas [KO:K07827]
103599614  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
103599723  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
103600170  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
103600324  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103600364  RRAS2; ras-related protein R-Ras2 [KO:K07830]
103600441  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103600583  ZFP36L1; zinc finger protein 36, C3H1 type-like 1 [KO:K18753]
103600669  SQSTM1; sequestosome-1 [KO:K14381]
103601062  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
103601244  [KO:K06640] [EC:2.7.11.1]
103601309  [KO:K02183]
103601310  CALML5; calmodulin-like protein 5 [KO:K02183]
103601365  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103601775  NBN; nibrin [KO:K10867]
103601972  PPID; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
103601992  [KO:K02183]
103602232  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
103602353  [KO:K06751]
103602373  CCNA1; cyclin-A1 [KO:K06627]
103602482  [KO:K21770]
103602744  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103602866  E2F4; transcription factor E2F4 [KO:K04682]
103602907  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103603077  [KO:K04851]
103603319  HUS1; checkpoint protein HUS1 [KO:K10903]
103603496  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
103603724  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
103603964  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103604133  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
103604521  PPP3R2; calcineurin subunit B type 2 isoform X1 [KO:K06268]
103604625  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
103604901  SERPINE1; plasminogen activator inhibitor 1 isoform X1 [KO:K03982]
103605434  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
103605698  [KO:K04456] [EC:2.7.11.1]
103606064  [KO:K06751]
103606198  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
103607082  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103607210  [KO:K04682]
103607297  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
103607313  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103607428  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607442  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607537  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103607967  [KO:K06269] [EC:3.1.3.16]
103608004  CCNA2; cyclin-A2 [KO:K06627]
103608454  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103608705  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103608706  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
103608913  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
103608978  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
103609174  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103609219  [KO:K06751]
103609904  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
103610244  [KO:K06751]
103610513  HRAS; GTPase HRas isoform X1 [KO:K02833]
103610546  [KO:K02830] [EC:3.1.11.2]
103610772  [KO:K06751]
103610793  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
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
gvr04020  Calcium signaling pathway
gvr04068  FoxO signaling pathway
gvr04110  Cell cycle
gvr04115  p53 signaling pathway
gvr04150  mTOR signaling pathway
KO pathway
ko04218   

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