KEGG   PATHWAY: acun04218
Entry
acun04218                   Pathway                                
Name
Cellular senescence - Athene cunicularia (burrowing owl)
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
acun04218  Cellular senescence
acun04218

Other DBs
GO: 0090398
Organism
Athene cunicularia (burrowing owl) [GN:acun]
Gene
113478516  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
113480465  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
113476683  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
113477102  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
113482298  TGF-beta receptor type-2-like isoform X1 [KO:K04388] [EC:2.7.11.30]
113489639  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
113484131  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
113476723  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
113481227  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
113488829  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
113489292  RB1; retinoblastoma-associated protein [KO:K06618]
113490673  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
113484278  RBL2; retinoblastoma-like protein 2 [KO:K16332]
113488364  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
113477352  E2F3; transcription factor E2F3 [KO:K06620]
113476539  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
113484493  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
113487938  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113483286  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113483483  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
113483193  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113489298  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113489600  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113482931  FOXO1; forkhead box protein O1 [KO:K07201]
113478153  FOXO3; forkhead box protein O3 [KO:K09408]
113488931  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
113491306  CDKN1B; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1B [KO:K06625]
113476163  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
113484462  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
113490617  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
113491163  KRAS; GTPase KRas isoform X1 [KO:K07827]
113488912  NRAS; GTPase NRas [KO:K07828]
113481185  RRAS2; ras-related protein R-Ras2 [KO:K07830]
113482327  MRAS; ras-related protein M-Ras [KO:K07831]
113481169  HRAS; GTPase HRas [KO:K02833]
113477826  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113490822  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
113480539  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
113486658  TSC1; hamartin isoform X1 [KO:K07206]
113485670  TSC2; tuberin isoform X1 [KO:K07207]
113477285  RHEB; GTP-binding protein Rheb [KO:K07208]
113487804  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
113481870  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]
113481816  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
113487595  CCNA1; cyclin-A1 [KO:K06627]
113479643  CCNA2; cyclin-A2 [KO:K06627]
113487466  MYBL2; myb-related protein B [KO:K21769]
113478776  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
113480472  LIN52; protein lin-52 homolog [KO:K21775]
113479517  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
113488272  RBBP4; histone-binding protein RBBP4 [KO:K10752]
113491301  FOXM1; forkhead box protein M1 [KO:K09406]
113476188  MYC; myc proto-oncogene protein [KO:K04377]
113490049  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
113488841  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
113485119  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
113481483  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
113481294  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
113490819  HIPK4; LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
113489855  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
113488884  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
113486130  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
113478943  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
113484728  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
113484193  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113489457  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113486052  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113488542  ETS1; protein C-ets-1 [KO:K02678]
113485588  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
113486793  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
113491236  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
113491286  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
113488967  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
113488974  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
113490088  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
113481880  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
113489650  CCNB1; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1 [KO:K05868]
113484014  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
113480066  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
113479965  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
113485244  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
113476159  NBN; nibrin [KO:K10867]
113478019  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
113486115  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
113486101  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
113489548  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
113476261  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
113483535  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
113488427  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
113476811  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
113485050  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
113478260  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
113478857  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
113479867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113476314  IL6; interleukin-6 [KO:K05405]
113479570  interleukin-8-like [KO:K10030]
113479571  interleukin-8-like [KO:K10030]
113479572  interleukin-8-like [KO:K10030]
113477277  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
113488889  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:2.7.11.1]
113480829  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
113484825  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
113483902  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
113478451  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
113477955  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
113480730  CALM1; calmodulin-1 [KO:K02183]
113483879  CALML4; calmodulin-like protein 4 [KO:K02183]
113489985  calmodulin, striated muscle [KO:K02183]
113478482  CALM2; calmodulin-2 [KO:K02183]
113481752  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
113490863  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
113479547  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
113478143  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
113477100  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
113487551  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
113484543  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
113484753  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
113489114  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
113488982  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
113480143  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
113479234  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
113478665  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
113479703  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
113485107  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
113481457  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
113488093  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
113481825  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
acun04020  Calcium signaling pathway
acun04068  FoxO signaling pathway
acun04110  Cell cycle
acun04115  p53 signaling pathway
acun04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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