KEGG   PATHWAY: afor04218
Entry
afor04218                   Pathway                                
Name
Cellular senescence - Aptenodytes forsteri (emperor penguin)
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
afor04218  Cellular senescence
afor04218

Other DBs
GO: 0090398
Organism
Aptenodytes forsteri (emperor penguin) [GN:afor]
Gene
103896919  TGFB2; transforming growth factor beta-2 [KO:K13376]
103900124  TGFB3; transforming growth factor beta-3 [KO:K13377]
103907675  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
103908596  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
103906690  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
103898213  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103899850  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103895923  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103904929  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103906574  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103893621  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
103903669  retinoblastoma-associated protein [KO:K06618]
103902230  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103896865  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103902903  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
103896399  transcription factor E2F2 [KO:K09389]
103894551  E2F3; transcription factor E2F3 [KO:K06620]
103896241  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
103908396  E2F4; transcription factor E2F4 [KO:K04682]
103906182  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103894035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103907467  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103899302  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103905595  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
103893369  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103907985  FOXO1; forkhead box protein O1 [KO:K07201]
103898789  FOXO3; forkhead box protein O3 [KO:K09408]
103908252  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103906559  cyclin-dependent kinase inhibitor 1 [KO:K06625]
103895771  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103900381  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
103898696  KRAS; GTPase KRas isoform X1 [KO:K07827]
103893660  NRAS; GTPase NRas [KO:K07828]
103906750  RRAS2; ras-related protein R-Ras2 [KO:K07830]
103895393  MRAS; ras-related protein M-Ras [KO:K07831]
103896209  HRAS; GTPase HRas [KO:K02833]
103896250  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103900090  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103900238  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103905322  TSC1; hamartin isoform X1 [KO:K07206]
103904934  TSC2; tuberin isoform X1 [KO:K07207]
103906000  RHEB; GTP-binding protein Rheb [KO:K07208]
103907452  MTOR; serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
103895482  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]
103908229  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
103907360  CCNA2; cyclin-A2 [KO:K06627]
103907991  CCNA1; cyclin-A1 [KO:K06627]
103895839  MYBL2; myb-related protein B [KO:K21769]
103904170  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
103900107  LIN52; protein lin-52 homolog [KO:K21775]
103902597  LIN54; protein lin-54 homolog [KO:K21776]
103903559  RBBP4; histone-binding protein RBBP4 [KO:K10752]
103908534  FOXM1; forkhead box protein M1 [KO:K09406]
103893925  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103893590  RASSF5; ras association domain-containing protein 5 [KO:K08015]
103897696  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
103893903  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
103893556  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
103900088  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
103906456  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
103906793  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
103902648  PPP1CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103902776  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103905412  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
103899919  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103900480  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103900168  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103893768  ETS1; protein C-ets-1 [KO:K02678]
103904894  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
103902435  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103905253  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103905254  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103893653  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
103893654  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103898473  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
103899397  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103900885  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103908178  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103893417  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103899878  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103901303  MRE11; double-strand break repair protein MRE11A isoform X1 [KO:K10865]
103904450  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
103895751  NBN; nibrin [KO:K10867]
103897009  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
103901854  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
103902780  RAD9B; LOW QUALITY PROTEIN: cell cycle checkpoint control protein RAD9B [KO:K10995]
103903914  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
103907616  HUS1; checkpoint protein HUS1 [KO:K10903]
103905126  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
103903477  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
103904394  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
103906889  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
103907055  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
103894216  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
103901234  IL6; interleukin-6 [KO:K05405]
103898933  C-X-C motif chemokine 5-like [KO:K10030]
103898934  interleukin-8 isoform X1 [KO:K10030]
103898935  interleukin-8 [KO:K10030]
103904018  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
103893587  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103898913  ZFP36L1; LOW QUALITY PROTEIN: mRNA decay activator protein ZFP36L1 [KO:K18753]
103903298  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103902750  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
103896708  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103902673  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
103894552  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
103894459  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103904815  CALM2; calmodulin [KO:K02183]
103899913  CALML4; calmodulin-like protein 4 [KO:K02183]
103900156  calmodulin [KO:K02183]
103901743  calmodulin, striated muscle [KO:K02183]
103894276  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
103897605  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
103904663  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103908533  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
103897208  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
103894642  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
103896873  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
103902541  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103898700  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103893713  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103895696  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
103897367  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
103907349  SLC25A31; LOW QUALITY PROTEIN: ADP/ATP translocase 4 [KO:K05863]
103900665  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
103902329  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
103904440  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
103897578  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
103898505  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
103895515  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
afor04020  Calcium signaling pathway
afor04068  FoxO signaling pathway
afor04110  Cell cycle
afor04115  p53 signaling pathway
afor04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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