KEGG   PATHWAY: egz04218
Entry
egz04218                    Pathway                                
Name
Cellular senescence - Egretta garzetta (little egret)
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
egz04218  Cellular senescence
egz04218

Other DBs
GO: 0090398
Organism
Egretta garzetta (little egret) [GN:egz]
Gene
104133428  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
104133279  TGFB3; transforming growth factor beta-3 [KO:K13377]
104125437  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
104122957  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
104128099  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
104134175  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
104125236  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
104128955  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104124693  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104124210  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
104125735  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
104131621  RB1; retinoblastoma-associated protein [KO:K06618]
104125514  RBL1; retinoblastoma-like protein 1 [KO:K04681]
104125194  RBL2; retinoblastoma-like protein 2 [KO:K16332]
104124989  E2F1; transcription factor E2F1 [KO:K17454]
104132520  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
104125451  E2F3; transcription factor E2F3 [KO:K06620]
104123576  E2F5; transcription factor E2F5 [KO:K04682]
104130313  E2F4; transcription factor E2F4 [KO:K04682]
104133065  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104135481  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104129991  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104135641  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
104124880  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104126253  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104129682  FOXO1; forkhead box protein O1 [KO:K07201]
104131578  FOXO3; forkhead box protein O3 [KO:K09408]
104131411  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
104124226  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104124192  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104125564  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
104125860  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
104135137  KRAS; GTPase KRas isoform X1 [KO:K07827]
104126779  NRAS; GTPase NRas [KO:K07828]
104123156  RRAS2; ras-related protein R-Ras2 [KO:K07830]
104131516  MRAS; ras-related protein M-Ras [KO:K07831]
104123569  HRAS; GTPase HRas [KO:K02833]
104131524  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104125648  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104128282  TSC1; hamartin isoform X1 [KO:K07206]
104127720  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
104130996  RHEB; GTP-binding protein Rheb [KO:K07208]
104133077  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104125131  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]
104124613  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
104129322  CCNA2; cyclin-A2 [KO:K06627]
104131327  CCNA1; cyclin-A1 [KO:K06627]
104132165  MYBL2; myb-related protein B [KO:K21769]
104134610  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
104133240  LIN52; protein lin-52 homolog [KO:K21775]
104133988  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
104134921  RBBP4; histone-binding protein RBBP4 [KO:K10752]
104128883  FOXM1; forkhead box protein M1 [KO:K09406]
104134424  MYC; myc proto-oncogene protein [KO:K04377]
104132910  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104134352  RASSF5; ras association domain-containing protein 5 [KO:K08015]
104125612  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
104135945  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
104135573  HIPK2; LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
104126782  HIPK1; homeodomain-interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
104133509  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
104134734  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
104135633  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104122715  PPP1CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
104124306  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104133527  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104124397  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104127223  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104129204  ETS1; LOW QUALITY PROTEIN: protein C-ets-1 [KO:K02678]
104132608  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
104132828  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
104125693  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104125710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104125751  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104125670  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104126926  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104124647  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
104124904  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
104130767  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
104133018  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
104131715  MRE11A; double-strand break repair protein MRE11A [KO:K10865]
104133508  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
104125806  NBN; nibrin [KO:K10867]
104130058  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
104122580  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
104122733  RAD9B; LOW QUALITY PROTEIN: cell cycle checkpoint control protein RAD9B [KO:K10995]
104133919  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
104125963  HUS1; checkpoint protein HUS1 [KO:K10903]
104127113  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
104129228  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
104121808  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
104123354  SQSTM1; LOW QUALITY PROTEIN: sequestosome-1 [KO:K14381]
104127261  GATA4; LOW QUALITY PROTEIN: transcription factor GATA-4 [KO:K09183]
104131980  TRAF3IP2; adapter protein CIKS [KO:K21124]
104122596  LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
104126108  IL6; interleukin-6 [KO:K05405]
104127742  interleukin-8-like [KO:K10030]
104127741  interleukin-8 [KO:K10030]
104127745  interleukin-8-like [KO:K10030]
104125967  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
104127858  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
104134508  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
104126731  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
104128379  TRPV4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 4 [KO:K04973]
104130794  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104132723  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
104124542  CAPN2; LOW QUALITY PROTEIN: calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
104135634  calmodulin-A isoform X1 [KO:K02183]
104135674  CALM1; calmodulin [KO:K02183]
104128388  CALML4; calmodulin-like protein 4 [KO:K02183]
104134827  LOW QUALITY PROTEIN: calmodulin, striated muscle-like [KO:K02183]
104129113  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
104127929  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
104122599  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
104129247  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
104125444  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
104132151  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
104125186  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
104132649  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
104135140  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104125774  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104125138  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
104129313  SLC25A31; LOW QUALITY PROTEIN: ADP/ATP translocase 4 [KO:K05863]
104129432  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
104124066  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
104124148  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
104133459  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104129097  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104135298  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104128410  MCU; LOW QUALITY PROTEIN: 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
egz04020  Calcium signaling pathway
egz04068  FoxO signaling pathway
egz04110  Cell cycle
egz04115  p53 signaling pathway
egz04150  mTOR signaling pathway
KO pathway
ko04218   
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