KEGG   PATHWAY: gfr04218
Entry
gfr04218                    Pathway                                
Name
Cellular senescence - Geospiza fortis (medium ground-finch)
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
gfr04218  Cellular senescence
gfr04218

Other DBs
GO: 0090398
Organism
Geospiza fortis (medium ground-finch) [GN:gfr]
Gene
102037698  TGFB2; transforming growth factor beta 2 [KO:K13376]
102037028  TGFB3; transforming growth factor beta 3 [KO:K13377]
102037879  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102044945  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
102040558  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102040865  mothers against decapentaplegic homolog 2-like [KO:K04500]
102044404  SMAD2; SMAD family member 2 [KO:K04500]
102040325  SMAD3; SMAD family member 3 [KO:K23605]
102034159  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102042858  CCND1; cyclin D1 [KO:K04503]
102034688  CCND2; cyclin D2 [KO:K10151]
102033692  CCND3; cyclin D3 [KO:K10152]
102036868  RB1; RB transcriptional corepressor 1 [KO:K06618]
102034865  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102044028  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102032688  E2F1; E2F transcription factor 1 [KO:K17454]
102036661  E2F2; transcription factor E2F2 [KO:K09389]
102039591  E2F3; E2F transcription factor 3 [KO:K06620]
102032445  E2F4; E2F transcription factor 4 [KO:K04682]
102037886  E2F5; E2F transcription factor 5 [KO:K04682]
102042284  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102040845  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102040853  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102039817  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102032353  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102035891  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102039410  FOXO1; forkhead box O1 [KO:K07201]
102034329  FOXO3; forkhead box O3 [KO:K09408]
102041135  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102043017  CCNE2; cyclin E2 [KO:K06626]
102040569  CCNE1; cyclin E1 [KO:K06626]
102039800  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
102034923  FCGRT; Fc fragment of IgG receptor and transporter [KO:K06751]
102035876  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102039955  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102033064  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102033145  MRAS; muscle RAS oncogene homolog [KO:K07831]
102044012  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102036745  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102036791  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102040493  TSC1; tuberous sclerosis 1 [KO:K07206]
102039715  TSC2; tuberous sclerosis 2 [KO:K07207]
102045581  RHEB; Ras homolog enriched in brain [KO:K07208]
102034190  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102039901  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102038978  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
102043650  CCNA1; cyclin A1 [KO:K06627]
102032849  CCNA2; cyclin A2 [KO:K06627]
102033718  MYBL2; MYB proto-oncogene like 2 [KO:K21769]
102041305  LIN9; lin-9 DREAM MuvB core complex component [KO:K21773]
102039911  LIN52; lin-52 DREAM MuvB core complex component [KO:K21775]
102040823  LIN54; lin-54 DREAM MuvB core complex component [KO:K21776]
102043913  RBBP4; RB binding protein 4, chromatin remodeling factor [KO:K10752]
102037453  FOXM1; forkhead box M1 [KO:K09406]
102041787  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102038761  RASSF5; Ras association domain family member 5 [KO:K08015]
102038820  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
102045368  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
102033832  HIPK2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
102036557  HIPK3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
102040739  HIPK4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102042492  HIPK1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
102032151  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102042078  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102039437  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102034977  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102031727  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102041148  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102043401  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102034475  ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678]
102039295  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102039445  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102043521  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102038787  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102044158  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102042160  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102034239  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102044449  CCNB2; cyclin B2 [KO:K21770]
102043430  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
102033534  MRE11; MRE11 homolog, double strand break repair nuclease [KO:K10865]
102037092  RAD50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
102045573  NBN; nibrin [KO:K10867]
102038788  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102039617  RAD9A; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
102041574  RAD9B; RAD9 checkpoint clamp component B [KO:K10995]
102036827  RAD1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
102039550  HUS1; HUS1 checkpoint clamp component [KO:K10903]
102032229  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102039036  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102040683  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102039289  SQSTM1; sequestosome 1 [KO:K14381]
102034959  GATA4; GATA binding protein 4 [KO:K09183]
102037476  TRAF3IP2; TRAF3 interacting protein 2 [KO:K21124]
102038208  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102040265  IL6; interleukin 6 [KO:K05405]
102038021  interleukin-8-like [KO:K10030]
102040521  interleukin-8-like [KO:K10030]
102040345  interleukin-8-like [KO:K10030]
102040735  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
102044089  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102033587  ZFP36L1; ZFP36 ring finger protein like 1 [KO:K18753]
102035179  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102037485  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102043510  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102035321  CAPN11; calpain 11 [KO:K01367] [EC:3.4.22.52]
102045030  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
102036454  CALM2; calmodulin 2 [KO:K02183]
102040647  CALM1; calmodulin 1 [KO:K02183]
102044755  calmodulin, striated muscle [KO:K02183]
102033217  CALML4; calmodulin like 4 [KO:K02183]
102037249  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102037137  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102039738  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102034017  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102038895  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102045241  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102038668  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102045318  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102036319  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102036728  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102031695  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
102038498  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
102039001  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
102035208  PPID; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
102038381  VDAC1; voltage dependent anion channel 1 [KO:K05862]
102038775  VDAC2; voltage dependent anion channel 2 [KO:K15040]
102034080  VDAC3; voltage dependent anion channel 3 [KO:K15041]
102041999  MCU; mitochondrial calcium uniporter [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
gfr04020  Calcium signaling pathway
gfr04068  FoxO signaling pathway
gfr04110  Cell cycle
gfr04115  p53 signaling pathway
gfr04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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