KEGG   PATHWAY: pvp04218
Entry
pvp04218                    Pathway                                
Name
Cellular senescence - Pteropus vampyrus (large flying fox)
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
pvp04218  Cellular senescence
pvp04218

Other DBs
GO: 0090398
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288383  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105288434  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
105288747  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
105288836  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
105288852  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105288878  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
105289213  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
105289220  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289599  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
105289962  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
105290127  CALM1; calmodulin-1 [KO:K02183]
105290449  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105290587  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105291571  GATA4; transcription factor GATA-4 [KO:K09183]
105291662  HIPK2; homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
105292082  RBL2; retinoblastoma-like protein 2 [KO:K16332]
105292339  CXCL8; interleukin-8 [KO:K10030]
105292451  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105292580  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
105292618  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
105292640  SMAD2; mothers against decapentaplegic homolog 2 isoform X3 [KO:K04500]
105292913  CALM2; calmodulin-2 isoform X1 [KO:K02183]
105292934  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293031  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105293112  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105293152  IL6; interleukin-6 isoform X2 [KO:K05405]
105293261  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105293290  CCNA1; cyclin-A1 [KO:K06627]
105293469  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
105293481  [KO:K06751]
105293548  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
105293648  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
105293923  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105294273  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294446  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
105294477  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
105294703  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
105294975  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105295227  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
105295250  FOXO3; forkhead box protein O3 [KO:K09408]
105295516  [KO:K05863]
105295781  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
105295887  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105296040  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
105296163  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105296245  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
105296266  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
105296511  RBL1; retinoblastoma-like protein 1 [KO:K04681]
105296533  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296599  HIPK1; homeodomain-interacting protein kinase 1 isoform X2 [KO:K08826] [EC:2.7.11.1]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296813  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
105296858  ETS1; protein C-ets-1 [KO:K02678]
105297140  [KO:K02649]
105297274  FOXM1; forkhead box protein M1 isoform X2 [KO:K09406]
105297322  CALM3; calmodulin-3 [KO:K02183]
105297463  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
105297886  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
105297999  RELA; transcription factor p65 [KO:K04735]
105298268  MYBL2; myb-related protein B [KO:K21769]
105298440  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X4 [KO:K04685]
105298655  TSC1; hamartin isoform X1 [KO:K07206]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298804  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
105298901  FOXO1; forkhead box protein O1 [KO:K07201]
105298936  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299132  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
105299180  [KO:K02183]
105299206  TGFB3; transforming growth factor beta-3 [KO:K13377]
105299237  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
105299298  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299725  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
105299974  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
105300023  RB1; retinoblastoma-associated protein [KO:K06618]
105300158  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
105300159  [KO:K04456] [EC:2.7.11.1]
105300185  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
105300252  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105300424  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105300538  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
105300647  RASSF5; ras association domain-containing protein 5 [KO:K08015]
105300942  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105301329  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105301479  RRAS2; ras-related protein R-Ras2 [KO:K07830]
105301705  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
105301735  RRAS; ras-related protein R-Ras [KO:K07829]
105301890  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
105302217  CCNA2; cyclin-A2 [KO:K06627]
105302354  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
105302600  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105302747  E2F5; transcription factor E2F5 [KO:K04682]
105303020  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
105303335  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
105303606  CALML6; calmodulin-like protein 6 [KO:K02183]
105303777  RHEB; GTP-binding protein Rheb [KO:K07208]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105303963  TRPV4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 4 [KO:K04973]
105303981  IL1A; interleukin-1 alpha [KO:K04383]
105304154  NBN; nibrin [KO:K10867]
105304165  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105304277  E2F1; transcription factor E2F1 [KO:K17454]
105304363  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304642  BTRC; F-box/WD repeat-containing protein 1A isoform X3 [KO:K03362]
105305341  [KO:K06751]
105305546  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
105305708  E2F4; transcription factor E2F4 [KO:K04682]
105305747  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
105305870  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306613  HUS1; checkpoint protein HUS1 [KO:K10903]
105306652  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105307128  [KO:K04503]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307393  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307945  TGFB1; transforming growth factor beta-1 [KO:K13375]
105308002  [KO:K05863]
105308067  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
105308283  [KO:K04441] [EC:2.7.11.24]
105308301  [KO:K10138]
105308799  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105308925  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:2.7.11.1]
105308953  [KO:K07831]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309333  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
105309403  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
105309601  [KO:K06751]
105309689  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105309746  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105309848  [KO:K06751]
105309864  [KO:K06751]
105309923  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
105309924  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
105309963  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
105310129  [KO:K06751]
105311216  [KO:K04685]
105311725  [KO:K06751]
105311774  [KO:K10138]
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
pvp04020  Calcium signaling pathway
pvp04068  FoxO signaling pathway
pvp04110  Cell cycle
pvp04115  p53 signaling pathway
pvp04150  mTOR signaling pathway
KO pathway
ko04218   

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