KEGG   PATHWAY: ccae04218
Entry
ccae04218                   Pathway                                
Name
Cellular senescence - Cyanistes caeruleus (blue tit)
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
ccae04218  Cellular senescence
ccae04218

Other DBs
GO: 0090398
Organism
Cyanistes caeruleus (blue tit) [GN:ccae]
Gene
111922139  [KO:K06751]
111922308  E2F5; transcription factor E2F5 [KO:K04682]
111922477  [KO:K06751]
111922589  [KO:K04456] [EC:2.7.11.1]
111922851  CCNA1; cyclin-A1 [KO:K06627]
111922987  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
111923053  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
111923171  [KO:K02183]
111923501  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
111923693  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
111923695  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
111923709  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
111923737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
111923921  [KO:K04446]
111924074  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
111924218  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
111924309  IL6; interleukin-6 [KO:K05405]
111924530  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
111924551  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
111924564  NBN; nibrin [KO:K10867]
111925128  MYC; myc proto-oncogene protein [KO:K04377]
111925444  RHEB; GTP-binding protein Rheb [KO:K07208]
111925581  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
111925972  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
111926211  TGFB2; transforming growth factor beta-2 [KO:K13376]
111926249  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
111926272  LIN9; protein lin-9 homolog [KO:K21773]
111926640  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
111927133  FOXO3; forkhead box protein O3 [KO:K09408]
111927156  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
111927487  [KO:K09183]
111927488  [KO:K09183]
111927556  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
111927570  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111927633  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
111927637  [KO:K02183]
111927739  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111927868  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
111928326  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
111928433  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
111928816  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
111929038  CCNA2; cyclin-A2 isoform X1 [KO:K06627]
111929290  [KO:K21771]
111929439  [KO:K10030]
111929465  [KO:K10030]
111929466  [KO:K10030]
111929574  LIN52; protein lin-52 homolog [KO:K21775]
111929760  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111929893  CALM1; calmodulin-1 [KO:K02183]
111929961  TGFB3; transforming growth factor beta-3 [KO:K13377]
111930014  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
111930045  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
111930282  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
111930464  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
111930555  RRAS2; ras-related protein R-Ras2 [KO:K07830]
111930656  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111930717  HRAS; GTPase HRas [KO:K02833]
111931054  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
111931085  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111931254  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
111931455  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
111931513  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
111931551  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
111931632  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]
111932216  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
111932269  [KO:K04388] [EC:2.7.11.30]
111932718  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
111933104  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111933356  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111933508  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
111933753  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111933879  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
111933962  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
111933966  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111934176  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
111934599  RBL2; LOW QUALITY PROTEIN: retinoblastoma-like protein 2 [KO:K16332]
111934658  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
111934756  E2F4; transcription factor E2F4 [KO:K04682]
111934774  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
111934931  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
111935128  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111935240  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111935553  SQSTM1; sequestosome-1 [KO:K14381]
111935601  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
111935623  RAD50; LOW QUALITY PROTEIN: DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
111935686  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
111936127  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
111936184  TSC2; tuberin isoform X1 [KO:K07207]
111936332  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
111936412  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
111936476  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
111936534  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111936713  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
111936724  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
111937022  TSC1; hamartin isoform X1 [KO:K07206]
111937452  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
111938272  MYBL2; myb-related protein B [KO:K21769]
111938353  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
111938436  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
111938578  HIPK4; homeodomain-interacting protein kinase 4 isoform X1 [KO:K08826] [EC:2.7.11.1]
111938583  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
111938683  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111938823  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111938847  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
111938867  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
111938970  RBBP4; histone-binding protein RBBP4 [KO:K10752]
111939061  [KO:K09389]
111939252  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
111939380  ETS1; protein C-ets-1 [KO:K02678]
111939625  NRAS; GTPase NRas [KO:K07828]
111939739  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
111939790  RASSF5; ras association domain-containing protein 5 [KO:K08015]
111939795  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111939796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111939798  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111939850  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
111939904  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
111940193  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111940405  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111940949  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
111941053  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
111941370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111941727  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111941893  [KO:K06627]
111941945  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
111942470  [KO:K06751]
111942551  [KO:K13375]
111943688  [KO:K02183]
111943945  E2F1; transcription factor E2F1 [KO:K17454]
111944362  FOXO1; forkhead box protein O1 [KO:K07201]
111944386  [KO:K05863]
111944419  [KO:K10865]
111944525  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
111944533  RAD9A; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
111944648  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111944825  [KO:K06751]
111945032  [KO:K06751]
111945197  [KO:K06751]
111945773  KRAS; GTPase KRas isoform X1 [KO:K07827]
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
ccae04020  Calcium signaling pathway
ccae04068  FoxO signaling pathway
ccae04110  Cell cycle
ccae04115  p53 signaling pathway
ccae04150  mTOR signaling pathway
KO pathway
ko04218   

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