KEGG   PATHWAY: plet04218
Entry
plet04218                   Pathway                                
Name
Cellular senescence - Phaethon lepturus (White-tailed tropicbird)
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
plet04218  Cellular senescence
plet04218

Other DBs
GO: 0090398
Organism
Phaethon lepturus (White-tailed tropicbird) [GN:plet]
Gene
104619128  TGFB2; transforming growth factor beta-2 [KO:K13376]
104617813  TGFB3; transforming growth factor beta-3 [KO:K13377]
104619050  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
104617793  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
104621568  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
104622665  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
104619719  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
104626632  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104617292  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104616874  G1/S-specific cyclin-D2-like [KO:K10151]
104626904  G1/S-specific cyclin-D3-like [KO:K10152]
104624256  retinoblastoma-associated protein [KO:K06618]
104614320  RBL1; retinoblastoma-like protein 1 [KO:K04681]
104622012  RBL2; retinoblastoma-like protein 2 [KO:K16332]
104627607  E2F1; transcription factor E2F1 [KO:K17454]
104627683  E2F3; transcription factor E2F3 [KO:K06620]
104615513  E2F5; transcription factor E2F5 [KO:K04682]
104628445  E2F4; transcription factor E2F4 [KO:K04682]
104624332  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104620606  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104617346  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104621033  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104623180  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104618789  FOXO1; forkhead box protein O1 [KO:K07201]
104617432  FOXO3; forkhead box protein O3 [KO:K09408]
104616579  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104628025  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104616509  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
104626738  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
104615251  GTPase KRas [KO:K07827]
104617220  NRAS; GTPase NRas [KO:K07828]
104626430  RRAS2; ras-related protein R-Ras2 [KO:K07830]
104626956  MRAS; ras-related protein M-Ras [KO:K07831]
104623545  HRAS; GTPase HRas [KO:K02833]
104624254  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104622496  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104622682  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104617340  TSC1; hamartin isoform X1 [KO:K07206]
104624805  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
104620867  RHEB; GTP-binding protein Rheb [KO:K07208]
104621133  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104615309  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]
104617559  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
104620233  CCNA1; cyclin-A1 [KO:K06627]
104615136  CCNA2; cyclin-A2 [KO:K06627]
104620954  MYBL2; myb-related protein B [KO:K21769]
104614542  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
104617976  LIN52; protein lin-52 homolog [KO:K21775]
104617654  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
104626858  RBBP4; histone-binding protein RBBP4 [KO:K10752]
104618640  FOXM1; LOW QUALITY PROTEIN: forkhead box protein M1 [KO:K09406]
104625310  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104624919  RASSF5; ras association domain-containing protein 5 [KO:K08015]
104614773  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
104617734  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
104616650  LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 2-like [KO:K08826] [EC:2.7.11.1]
104626050  HIPK1; LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
104622046  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
104618943  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
104627645  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
104628260  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
104615600  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
104627321  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
104615077  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104625875  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104626425  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104622359  ETS1; LOW QUALITY PROTEIN: protein C-ets-1 [KO:K02678]
104626208  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
104623176  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
104618194  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
104618865  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
104618866  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104628347  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104622163  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104628265  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
104620335  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
104614647  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
104617091  MRE11A; double-strand break repair protein MRE11A [KO:K10865]
104627168  LOW QUALITY PROTEIN: DNA repair protein RAD50-like [KO:K10866] [EC:3.6.-.-]
104620049  NBN; nibrin [KO:K10867]
104622353  serine-protein kinase ATM-like [KO:K04728] [EC:2.7.11.1]
104614156  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
104619989  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
104614583  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
104626034  HUS1; checkpoint protein HUS1 [KO:K10903]
104624144  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
104614013  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
104625978  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
104626506  adapter protein CIKS-like [KO:K21124]
104621489  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104615743  IL6; interleukin-6 [KO:K05405]
104623935  interleukin-8-like isoform X1 [KO:K10030]
104623938  interleukin-8-like [KO:K10030]
104623939  interleukin-8-like [KO:K10030]
104617413  interleukin-8-like [KO:K10030]
104618421  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
104616995  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
104623800  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
104621806  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
104626874  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104622448  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
104620768  LOW QUALITY PROTEIN: calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
104613993  CALML4; calmodulin-like protein 4 [KO:K02183]
104626389  CALM2; calmodulin [KO:K02183]
104615665  LOW QUALITY PROTEIN: calmodulin-A-like [KO:K02183]
104622393  LOW QUALITY PROTEIN: calmodulin, striated muscle-like [KO:K02183]
104616455  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
104620701  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
104618858  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
104625866  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
104616890  nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446]
104620171  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
104627956  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
104626647  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 3-like [KO:K17333]
104619233  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
104628694  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
104615713  ADP/ATP translocase 3 [KO:K05863]
104615509  ADP/ATP translocase 2 [KO:K05863]
104619175  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
104616094  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
104627724  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104615693  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104615282  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
104619824  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
plet04020  Calcium signaling pathway
plet04068  FoxO signaling pathway
plet04110  Cell cycle
plet04115  p53 signaling pathway
plet04150  mTOR signaling pathway
KO pathway
ko04218   
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