KEGG   PATHWAY: ngi04218
Entry
ngi04218                    Pathway                                
Name
Cellular senescence - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi04218  Cellular senescence
ngi04218

Other DBs
GO: 0090398
Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103724463  [KO:K06751]
103724616  Calm1; calmodulin 1 [KO:K02183]
103724738  Calm3; calmodulin 3 [KO:K02183]
103724822  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103724977  Capn1; calpain 1 [KO:K01367] [EC:3.4.22.52]
103724994  Rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103725102  Lin9; lin-9 DREAM MuvB core complex component [KO:K21773]
103725210  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103725555  [KO:K06751]
103725581  Ppp1ca; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
103725583  Rad9a; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
103725745  Calm2; calmodulin 2 [KO:K02183]
103725801  Mre11; MRE11 homolog, double strand break repair nuclease [KO:K10865]
103725891  Ccnd3; cyclin D3 [KO:K10152]
103725934  Mapkapk2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103725938  Rassf5; Ras association domain family member 5 [KO:K08015]
103726095  Hipk2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
103726150  [KO:K21771]
103726219  Slc25a31; solute carrier family 25 member 31 [KO:K05863]
103726266  Capn2; calpain 2 [KO:K03853] [EC:3.4.22.53]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103726618  Vdac3; voltage dependent anion channel 3 [KO:K15041]
103726779  Rb1; RB transcriptional corepressor 1 [KO:K06618]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103727547  Ccnd2; cyclin D2 [KO:K10151]
103727554  Foxm1; forkhead box M1 [KO:K09406]
103727836  Smad2; SMAD family member 2 [KO:K04500]
103728037  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
103728077  Nfkb1; nuclear factor kappa B subunit 1 [KO:K02580]
103728817  Tgfb2; transforming growth factor beta 2 [KO:K13376]
103729208  [KO:K02183]
103729534  Nbn; nibrin [KO:K10867]
103729749  Vdac1; voltage dependent anion channel 1 [KO:K05862]
103729781  [KO:K06751]
103729783  [KO:K06751]
103729784  [KO:K06751]
103729790  [KO:K06751]
103729792  [KO:K06751]
103729936  Lin37; lin-37 DREAM MuvB core complex component [KO:K21774]
103730015  Gata4; GATA binding protein 4 [KO:K09183]
103730228  Ppp1cb; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103730663  [KO:K06621]
103730664  Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685]
103730891  Rbbp4; RB binding protein 4, chromatin remodeling factor [KO:K10752]
103731142  [KO:K06751]
103731335  Atm; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
103731674  Rbl2; RB transcriptional corepressor like 2 [KO:K16332]
103731904  [KO:K18753]
103731982  Ccna1; cyclin A1 [KO:K06627]
103732897  Mtor; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103733047  Trpm7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103733497  Serpine1; serpin family E member 1 [KO:K03982]
103733767  Sirt1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
103734750  Ppp3r1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
103734929  Hipk1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103734978  Nfatc3; nuclear factor of activated T-cells 3 [KO:K17333]
103735473  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103735474  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103735579  Chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
103735763  Nfatc2; nuclear factor of activated T-cells 2 [KO:K17332]
103735939  Rad1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
103736117  Cdk1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103736391  Zfp36l2; ZFP36 ring finger protein like 2 [KO:K18753]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103736807  Smad3; SMAD family member 3 [KO:K23605]
103736816  Calml4; calmodulin like 4 [KO:K02183]
103736926  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
103736944  Ppp3cb; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
103736958  Mcu; mitochondrial calcium uniporter [KO:K20858]
103737133  Calml5; calmodulin like 5 [KO:K02183]
103737134  Calml3; calmodulin like 3 [KO:K02183]
103737154  Ccnb2; cyclin B2 [KO:K21770]
103737157  E2f5; E2F transcription factor 5 [KO:K04682]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103737285  Gadd45b; growth arrest and DNA damage inducible beta [KO:K04402]
103737601  Mras; muscle RAS oncogene homolog [KO:K07831]
103738044  Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103738688  [KO:K06751]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103738717  Ccnb1; cyclin B1 [KO:K05868]
103738907  E2f4; E2F transcription factor 4 [KO:K04682]
103739085  Rad9b; RAD9 checkpoint clamp component B [KO:K10995]
103739088  Ppp1cc; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
103739356  [KO:K06751]
103739410  Nfatc4; nuclear factor of activated T-cells 4 [KO:K17334]
103739652  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
103739659  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103739660  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103739696  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103739777  Tgfb3; transforming growth factor beta 3 [KO:K13377]
103739898  Il1a; interleukin 1 alpha [KO:K04383]
103740578  [KO:K06751]
103740682  Ets1; ETS proto-oncogene 1, transcription factor [KO:K02678]
103740830  Ccne1; cyclin E1 [KO:K06626]
103740849  Il6; interleukin 6 [KO:K05405]
103741431  Igfbp3; insulin like growth factor binding protein 3 [KO:K10138]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103741482  Hus1; HUS1 checkpoint clamp component [KO:K10903]
103742218  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103742429  Cxcl8; C-X-C motif chemokine ligand 8 [KO:K10030]
103742835  Tsc1; tuberous sclerosis 1 [KO:K07206]
103742868  Slc25a5; solute carrier family 25 member 5 [KO:K05863]
103742900  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103743354  Gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
103743672  Rras; related RAS viral (r-ras) oncogene homolog [KO:K07829]
103743920  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103744000  Btrc; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
103744250  [KO:K06751]
103744639  Tgfbr2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
103744902  Tgfbr1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
103744988  Lin54; lin-54 DREAM MuvB core complex component [KO:K21776]
103745079  Mdm2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103745322  Rheb; Ras homolog enriched in brain [KO:K07208]
103745641  E2f3; E2F transcription factor 3 [KO:K06620]
103745830  Ccne2; cyclin E2 [KO:K06626]
103746411  E2f2; E2F transcription factor 2 [KO:K09389]
103746495  Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
103746703  Trpv4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103746957  Ccna2; cyclin A2 [KO:K06627]
103747027  Rad50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
103747066  Foxo1; forkhead box O1 [KO:K07201]
103747366  Lin52; lin-52 DREAM MuvB core complex component [KO:K21775]
103747445  Vdac2; voltage dependent anion channel 2 [KO:K15040]
103747869  Ppp3cc; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
103747894  [KO:K06751]
103747985  [KO:K15040]
103748128  Nfatc1; nuclear factor of activated T-cells 1 [KO:K04446]
103748186  Fbxw11; F-box and WD repeat domain containing 11 [KO:K03362]
103748374  Mybl2; MYB proto-oncogene like 2 [KO:K21769]
103748817  Hipk3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
103749025  Cacna1d; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
103749104  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
103749302  Zfp36l1; ZFP36 ring finger protein like 1 [KO:K18753]
103749374  Sqstm1; sequestosome 1 [KO:K14381]
103749535  Traf3ip2; TRAF3 interacting protein 2 [KO:K21124]
103749566  Foxo3; forkhead box O3 [KO:K09408]
103749800  Calml6; calmodulin like 6 [KO:K02183]
103750115  Slc25a6; solute carrier family 25 member 6 [KO:K05863]
103750230  Cdc25a; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
103750424  Rras2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
103750480  Slc25a4; solute carrier family 25 member 4 [KO:K05863]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103750760  Hipk4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
103750875  Chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
103751014  Ppid; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103751203  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103751225  Gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103751498  Ccnd1; cyclin D1 [KO:K04503]
103751514  Tgfb1; transforming growth factor beta 1 [KO:K13375]
103751571  E2f1; E2F transcription factor 1 [KO:K17454]
103752115  Tp53; tumor protein p53 [KO:K04451]
103752329  [KO:K06751]
103752451  Tsc2; tuberous sclerosis 2 [KO:K07207]
103752518  Atr; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
103752527  [KO:K06751]
103752528  [KO:K06751]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
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
ngi04020  Calcium signaling pathway
ngi04068  FoxO signaling pathway
ngi04110  Cell cycle
ngi04115  p53 signaling pathway
ngi04150  mTOR signaling pathway
KO pathway
ko04218   

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