KEGG   PATHWAY: gacu04218
Entry
gacu04218                   Pathway                                
Name
Cellular senescence - Gymnodraco acuticeps
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
gacu04218  Cellular senescence
gacu04218

Other DBs
GO: 0090398
Organism
Gymnodraco acuticeps [GN:gacu]
Gene
117532377  zfp36l1b; mRNA decay activator protein ZFP36L1b [KO:K18753]
117532535  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
117532612  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
117532640  [KO:K04503]
117532733  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
117532816  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
117532846  e2f1; transcription factor E2F1 [KO:K17454]
117532852  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
117532885  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
117533257  [KO:K04682]
117533657  [KO:K21770]
117533777  [KO:K13377]
117533810  gata4; transcription factor GATA-4 [KO:K09183]
117533824  lin9; protein lin-9 homolog [KO:K21773]
117533921  [KO:K21769]
117534213  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
117534230  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
117534275  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117534434  [KO:K01367] [EC:3.4.22.52]
117534598  ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
117534628  [KO:K04377]
117534701  [KO:K04348] [EC:3.1.3.16]
117534709  ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117534791  [KO:K06751]
117534799  [KO:K06751]
117535004  [KO:K02649]
117535110  ccna2; cyclin-A2 [KO:K06627]
117535131  ccna1; cyclin-A1 [KO:K06627]
117535208  [KO:K06626]
117535558  chek1; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
117535626  [KO:K03853] [EC:3.4.22.53]
117535767  trpv4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
117536300  [KO:K04960]
117536359  [KO:K04348] [EC:3.1.3.16]
117536453  hipk3b; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
117536478  [KO:K06751]
117536667  [KO:K06626]
117536788  si:dkey-251i10.1; ADP/ATP translocase 2 [KO:K05863]
117536909  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117537128  rras; ras-related protein R-Ras [KO:K07830]
117537131  [KO:K07830]
117537338  nfatc2a; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
117537646  slc25a5; ADP/ATP translocase 2 [KO:K05863]
117537754  slc25a4; ADP/ATP translocase 1 [KO:K05863]
117538439  rb1; retinoblastoma-associated protein [KO:K06618]
117538865  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117538911  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117538917  rad1; LOW QUALITY PROTEIN: cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
117539053  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A isoform X1 [KO:K06269] [EC:3.1.3.16]
117539059  rad9b; cell cycle checkpoint control protein RAD9B [KO:K10995]
117539593  [KO:K17332]
117539693  calm1a; calmodulin-1a [KO:K02183]
117539794  [KO:K06620]
117539925  rbl1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
117539972  tsc1b; TSC complex subunit 1b [KO:K07206]
117540204  rad50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
117540207  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
117540443  foxo1a; forkhead box protein O1-A [KO:K07201]
117540608  [KO:K21124]
117540774  [KO:K04443] [EC:2.7.11.1]
117540835  nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
117541129  rheb; GTP-binding protein Rheb [KO:K07208]
117541451  [KO:K06620]
117541518  e2f5; transcription factor E2F5 [KO:K04682]
117541859  cacna1db; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
117541887  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
117541966  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
117542198  mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
117542274  [KO:K02649]
117542348  ppp3r1a; calcineurin subunit B type 1 [KO:K06268]
117542378  [KO:K00922] [EC:2.7.1.153]
117542627  [KO:K04388] [EC:2.7.11.30]
117542722  rela; transcription factor p65 isoform X1 [KO:K04735]
117542738  serpine1; plasminogen activator inhibitor 1 [KO:K03982]
117542741  [KO:K06269] [EC:3.1.3.16]
117542821  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
117542826  e2f4; transcription factor E2F4 [KO:K04682]
117542925  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
117542926  [KO:K04402]
117542983  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
117543350  [KO:K15040]
117543405  [KO:K10030]
117543536  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117543700  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
117544100  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117544128  zgc:55558; GTPase HRas [KO:K07827]
117544558  [KO:K04456] [EC:2.7.11.1]
117544662  myca; transcriptional regulator Myc-A [KO:K04377]
117545022  ppp1cab; protein phosphatase 1, catalytic subunit, alpha isozyme b [KO:K06269] [EC:3.1.3.16]
117545167  [KO:K09408]
117545348  si:ch73-116o1.2; ras-related protein M-Ras isoform X1 [KO:K07831]
117545436  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
117545508  [KO:K00922] [EC:2.7.1.153]
117545568  [KO:K02649]
117545674  itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
117545716  kras; GTPase KRas isoform X1 [KO:K07827]
117545900  [KO:K02833]
117546153  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
117546339  ccnb3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
117546425  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117547244  rras2; ras-related protein R-Ras2 [KO:K07830]
117547434  hipk1a; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
117547509  mapk14b; LOW QUALITY PROTEIN: mitogen-activated protein kinase 14B [KO:K04441] [EC:2.7.11.24]
117547517  mapkapk2a; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
117547518  rassf5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
117548197  cacna1da; calcium channel, voltage-dependent, L type, alpha 1D subunit, a isoform X1 [KO:K04851]
117548389  [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
117548459  ccndx; cyclin Dx [KO:K10151]
117548532  cdk21; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117548594  [KO:K04433] [EC:2.7.12.2]
117548669  ppp1caa; protein phosphatase 1, catalytic subunit, alpha isozyme a [KO:K06269] [EC:3.1.3.16]
117548936  [KO:K06269] [EC:3.1.3.16]
117549139  [KO:K04681]
117549326  calml4a; calmodulin-like protein 4a isoform X1 [KO:K02183]
117549346  smad3a; mothers against decapentaplegic homolog 3a isoform X1 [KO:K23605]
117549809  lin52; protein lin-52 homolog [KO:K21775]
117549945  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117550034  akt1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117550112  [KO:K10752]
117550770  hipk2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
117550850  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
117550887  [KO:K04402]
117551026  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
117551047  [KO:K04958]
117551118  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
117551161  rhebl1; ras homolog, mTORC1 binding like 1 [KO:K07208]
117551297  zgc:56235; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15041]
117551661  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
117551707  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117551708  ets1; LOW QUALITY PROTEIN: protein C-ets-1 [KO:K02678]
117551767  ccnp; cyclin N-terminal domain-containing protein 2 isoform X1 [KO:K21770]
117551852  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
117551925  zfp36l2; mRNA decay activator protein ZFP36L2 [KO:K18753]
117551945  ppp3r1b; calcineurin subunit B type 1b [KO:K06268]
117552177  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
117552207  mre11a; double-strand break repair protein MRE11 [KO:K10865]
117552283  zgc:114130; mRNA decay activator protein ZFP36L1 [KO:K18753]
117552299  [KO:K04348] [EC:3.1.3.16]
117552316  [KO:K06751]
117552416  foxm1; LOW QUALITY PROTEIN: forkhead box protein M1 [KO:K09406]
117552426  sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
117552612  [KO:K04960]
117552767  tp53; cellular tumor antigen p53 [KO:K04451]
117553001  capn1a; calpain 1, (mu/I) large subunit a [KO:K01367] [EC:3.4.22.52]
117553009  [KO:K03853] [EC:3.4.22.53]
117553016  [KO:K03853] [EC:3.4.22.53]
117553527  map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
117553600  ppid; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
117553822  [KO:K04446]
117553893  nbn; nibrin [KO:K10867]
117553895  [KO:K04388] [EC:2.7.11.30]
117553916  [KO:K06269] [EC:3.1.3.16]
117553973  lin37; protein lin-37 homolog isoform X1 [KO:K21774]
117554187  [KO:K02183]
117554630  [KO:K10752]
117554769  [KO:K04500]
117555322  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
117555502  capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
117555508  tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
117555523  cxcl19; C-X-C motif chemokine 19 [KO:K10030]
117555603  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
117555793  fbxw11a; F-box/WD repeat-containing protein 11a isoform X1 [KO:K03362]
117555880  rad9a; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
117555971  foxo3b; forkhead box protein O3B [KO:K09408]
117556404  e2f2; transcription factor E2F2 [KO:K09389]
117556701  nfatc3a; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
117557150  traf3ip2a; adapter protein CIKS [KO:K21124]
117557203  [KO:K04682]
117557335  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
117557577  mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
117557599  [KO:K08826] [EC:2.7.11.1]
117557835  [KO:K21770]
117557839  [KO:K21770]
117558263  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
117558466  [KO:K10138]
117558516  [KO:K01367] [EC:3.4.22.52]
117558532  [KO:K01367] [EC:3.4.22.52]
117558642  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
117558700  rbbp4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
117558768  atr; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
117558798  [KO:K05868]
117558809  [KO:K05868]
117558830  zfp36l1a; mRNA decay activator protein ZFP36L1a [KO:K18753]
117558967  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
117558996  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
117559178  [KO:K10151]
117559326  nfatc1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
117559927  foxo6b; forkhead box protein O6b isoform X1 [KO:K09408]
117560397  [KO:K04456] [EC:2.7.11.1]
117560493  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
117560551  igfbp3; insulin-like growth factor-binding protein 3 [KO:K10138]
117560597  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
117560694  [KO:K18753]
117560712  [KO:K21124]
117560747  akt3a; LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117560847  ptena; phosphatase and tensin homolog A isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
117560888  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
117560996  [KO:K07205]
117561357  [KO:K08826] [EC:2.7.11.1]
117561441  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117561525  lin54; protein lin-54 homolog [KO:K21776]
117561619  tsc2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
117562423  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
117562483  [KO:K01367] [EC:3.4.22.52]
117562573  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
117562577  [KO:K04441] [EC:2.7.11.24]
117562657  [KO:K07201]
117562823  [KO:K05405]
117562828  cdk6; LOW QUALITY PROTEIN: cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
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
gacu04020  Calcium signaling pathway
gacu04068  FoxO signaling pathway
gacu04110  Cell cycle
gacu04115  p53 signaling pathway
gacu04150  mTOR signaling pathway
KO pathway
ko04218   

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