KEGG   PATHWAY: tup04218
Entry
tup04218                    Pathway                                
Name
Cellular senescence - Tupaia chinensis (Chinese tree shrew)
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
tup04218  Cellular senescence
tup04218

Other DBs
GO: 0090398
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102468121  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102468234  MRAS; muscle RAS oncogene homolog [KO:K07831]
102468317  CCNE1; cyclin E1 [KO:K06626]
102468332  MCU; mitochondrial calcium uniporter [KO:K20858]
102468681  CALML6; calmodulin like 6 [KO:K02183]
102468887  LIN54; lin-54 DREAM MuvB core complex component [KO:K21776]
102469176  [KO:K06269] [EC:3.1.3.16]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469729  [KO:K05863]
102470116  MYBL2; MYB proto-oncogene like 2 [KO:K21769]
102470597  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
102471344  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472462  CALM1; calmodulin 1 [KO:K02183]
102472695  [KO:K21771]
102472893  HIPK4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102473125  [KO:K06751]
102473158  SMAD3; SMAD family member 3 [KO:K23605]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102473924  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102474096  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102474732  NBN; nibrin [KO:K10867]
102474781  [KO:K06751]
102475396  CCNA2; cyclin A2 [KO:K06627]
102475560  IL1A; interleukin 1 alpha [KO:K04383]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102475617  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
102475973  CALML3; calmodulin-like protein 3 [KO:K02183]
102476316  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102476523  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102476565  HIPK2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
102476700  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102476721  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102476815  VDAC2; voltage dependent anion channel 2 [KO:K15040]
102477021  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
102477186  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102477414  [KO:K06751]
102478386  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102478468  SERPINE1; serpin family E member 1 [KO:K03982]
102478627  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102478641  RAD9A; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
102478659  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102478870  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102479093  ZFP36L1; ZFP36 ring finger protein like 1 [KO:K18753]
102479628  FOXO3; forkhead box O3 [KO:K09408]
102479669  E2F2; E2F transcription factor 2 [KO:K09389]
102479773  CALML5; calmodulin like 5 [KO:K02183]
102479902  CCND2; cyclin D2 [KO:K10151]
102480098  [KO:K05863]
102480757  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102480885  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102481120  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102481241  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102481301  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102481316  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
102481620  RASSF5; Ras association domain family member 5 [KO:K08015]
102481636  HUS1; HUS1 checkpoint clamp component [KO:K10903]
102481989  CCNB1; cyclin B1 [KO:K05868]
102482054  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102482093  [KO:K06751]
102482195  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102482323  GATA4; GATA binding protein 4 [KO:K09183]
102482369  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102482492  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102482985  E2F4; E2F transcription factor 4 [KO:K04682]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102483474  TSC1; tuberous sclerosis 1 [KO:K07206]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102483795  CALML4; calmodulin like 4 [KO:K02183]
102483908  ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678]
102483974  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102484276  TSC2; tuberous sclerosis 2 [KO:K07207]
102484296  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102484707  [KO:K02183]
102484770  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102484828  ZFP36L2; ZFP36 ring finger protein like 2 [KO:K18753]
102484832  E2F1; E2F transcription factor 1 [KO:K17454]
102484993  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102485164  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
102485262  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102485453  VDAC1; voltage dependent anion channel 1 [KO:K05862]
102485493  [KO:K02183]
102485966  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102486273  HIPK3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
102486518  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102486561  CCNB3; cyclin B3 [KO:K21771]
102486777  FOXM1; forkhead box M1 [KO:K09406]
102487106  PPID; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102487603  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102488121  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
102488284  LIN52; lin-52 DREAM MuvB core complex component [KO:K21775]
102488432  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102488445  LIN37; lin-37 DREAM MuvB core complex component [KO:K21774]
102488524  TGFB1; transforming growth factor beta 1 [KO:K13375]
102488724  LIN9; lin-9 DREAM MuvB core complex component [KO:K21773]
102489041  MRE11; MRE11 homolog, double strand break repair nuclease [KO:K10865]
102489114  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102489331  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102489658  FOXO1; forkhead box O1 [KO:K07201]
102489925  CCNA1; cyclin A1 [KO:K06627]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102490323  [KO:K06751]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102490572  [KO:K06751]
102490651  CCND1; cyclin D1 [KO:K04503]
102490747  [KO:K06751]
102490996  [KO:K05405]
102491278  HIPK1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
102491386  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
102492088  CCNE2; cyclin E2 [KO:K06626]
102492170  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102493041  CALM3; calmodulin 3 [KO:K02183]
102493190  CALM2; calmodulin 2 [KO:K02183]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102493291  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102493892  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
102494250  [KO:K06751]
102494657  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
102495258  CALMODULIN; calmodulin-alpha [KO:K02183]
102495591  RAD50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
102495693  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102495801  [KO:K04685]
102496137  IL6; interleukin-6 [KO:K05405]
102496329  RRAS2; ras-related protein R-Ras2 [KO:K07830]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102496861  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102496931  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102496941  [KO:K06751]
102497029  TGFB3; transforming growth factor beta 3 [KO:K13377]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102497506  [KO:K06751]
102497868  TRAF3IP2; TRAF3 interacting protein 2 [KO:K21124]
102498127  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102498598  SQSTM1; sequestosome 1 [KO:K14381]
102498982  [KO:K05868]
102499416  E2F3; E2F transcription factor 3 [KO:K06620]
102499419  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102499507  RB1; RB transcriptional corepressor 1 [KO:K06618]
102499541  SMAD2; SMAD family member 2 [KO:K04500]
102499577  CCND3; cyclin D3 [KO:K10152]
102500015  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102500283  RAD9B; RAD9 checkpoint clamp component B [KO:K10995]
102500294  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
102500482  TGFB2; transforming growth factor beta 2 [KO:K13376]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500761  RBBP4; RB binding protein 4, chromatin remodeling factor [KO:K10752]
102500872  E2F5; E2F transcription factor 5 [KO:K04682]
102501319  CCNB2; cyclin B2 [KO:K21770]
102501374  [KO:K06751]
102501733  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102502093  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102502516  RHEB; Ras homolog enriched in brain [KO:K07208]
102502643  [KO:K06751]
102502813  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102502852  RAD1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
102503238  TP53; tumor protein p53 [KO:K04451]
102503299  VDAC3; voltage dependent anion channel 3 [KO:K15041]
106733357  [KO:K05405]
106733358  [KO:K05405]
106733575  [KO:K05405]
106733746  [KO:K05405]
106733924  [KO:K04982] [EC:2.7.11.1]
106734036  [KO:K07830]
106734037  [KO:K05405]
106734038  [KO:K05405]
106734039  [KO:K05405]
106734889  [KO:K21775]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup04020  Calcium signaling pathway
tup04068  FoxO signaling pathway
tup04110  Cell cycle
tup04115  p53 signaling pathway
tup04150  mTOR signaling pathway
KO pathway
ko04218   

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