KEGG   PATHWAY: bta04218
Entry
bta04218                    Pathway                                
Name
Cellular senescence - Bos taurus (cow)
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
bta04218  Cellular senescence
bta04218

Other DBs
GO: 0090398
Organism
Bos taurus (cow) [GN:bta]
Gene
282089  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
534069  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
538957  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
282382  TGFBR1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
535376  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
516010  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
515125  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
527124  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
510618  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
511754  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
524530  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
615414  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
540547  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
534712  RB1; retinoblastoma-associated protein [KO:K06618]
524870  RBL1; retinoblastoma-like protein 1 [KO:K04681]
533294  RBL2; retinoblastoma-like protein 2 [KO:K16332]
535369  E2F1; transcription factor E2F1 [KO:K17454]
617024  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
541184  E2F3; transcription factor E2F3 [KO:K06620]
525428  E2F4; transcription factor E2F4 [KO:K04682]
539427  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
282306  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
517948  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
504531  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
282308  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
286865  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
282307  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
506618  FOXO1; forkhead box protein O1 [KO:K07201]
535530  FOXO3; forkhead box protein O3 [KO:K09408]
513497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
519217  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
533526  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
538436  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
407173  JSP.1; MHC Class I JSP.1 precursor [KO:K06751]
512672  major histocompatibility complex, class I precursor [KO:K06751]
515712  BOLA; MHC class I heavy chain isoform 1 precursor [KO:K06751]
767904  MGC126945; LOW QUALITY PROTEIN: uncharacterized protein LOC767904 [KO:K06751]
507917  BOLA class I histocompatibility antigen, alpha chain BL3-6 isoform X1 [KO:K06751]
510417  BOLA-NC1; non-classical MHC class I antigen precursor [KO:K06751]
533050  BoLA; major histocompatibility complex, class I, A precursor [KO:K06751]
616942  major histocompatibility complex, class I, A-like precursor [KO:K06751]
541140  KRAS; GTPase KRas [KO:K07827]
506322  NRAS; GTPase NRas [KO:K07828]
616503  RRAS; ras-related protein R-Ras [KO:K07829]
519269  RRAS2; ras-related protein R-Ras2 [KO:K07830]
540803  MRAS; ras-related protein M-Ras [KO:K07831]
100298939  HRAS; GTPase HRas isoform 1 [KO:K02833]
100847184  GTPase HRas-like [KO:K02833]
534923  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
280991  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100137872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
533440  TSC1; hamartin isoform X1 [KO:K07206]
504985  TSC2; tuberin isoform X9 [KO:K07207]
528204  RHEB; GTP-binding protein Rheb [KO:K07208]
100139219  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
540786  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]
613629  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
281667  CCNA2; cyclin-A2 [KO:K06627]
521939  CCNA1; cyclin-A1 [KO:K06627]
510420  MYBL2; myb-related protein B [KO:K21769]
534587  LIN9; protein lin-9 homolog [KO:K21773]
534550  LIN37; protein lin-37 homolog [KO:K21774]
618104  LIN52; protein lin-52 homolog [KO:K21775]
100139053  LIN54; protein lin-54 homolog [KO:K21776]
767940  RBBP4; histone-binding protein RBBP4 [KO:K10752]
790218  LOW QUALITY PROTEIN: histone-binding protein RBBP4-like [KO:K10752]
513643  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
511077  MYC; myc proto-oncogene protein [KO:K04377]
616369  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X2 [KO:K06621]
540378  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
281542  TP53; cellular tumor antigen p53 [KO:K04451]
539767  RASSF5; ras association domain-containing protein 5 [KO:K08015]
534072  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
540642  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
512233  HIPK1; homeodomain-interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
538866  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
520157  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
510158  HIPK2; homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
282318  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
516175  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
538829  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
521196  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
533199  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101905399  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
510434  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
540313  ETS1; protein C-ets-1 [KO:K02678]
516039  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
286883  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
534492  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
535327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
512943  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
618906  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
504939  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
618405  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
505463  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
281061  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
327679  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
132345077  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1-like [KO:K05868]
281668  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
100301478  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
525093  MRE11; double-strand break repair protein MRE11 [KO:K10865]
788127  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
522943  NBN; nibrin [KO:K10867]
526824  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
518897  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
504647  RAD9A; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
616597  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
518502  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
514142  HUS1; checkpoint protein HUS1 [KO:K10903]
504869  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
513678  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
520188  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
338045  SQSTM1; sequestosome-1 [KO:K14381]
327716  GATA4; transcription factor GATA-4 [KO:K09183]
616801  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
616115  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
508233  RELA; transcription factor p65 [KO:K04735]
281250  IL1A; interleukin-1 alpha precursor [KO:K04383]
280826  IL6; interleukin-6 precursor [KO:K05405]
280828  CXCL8; interleukin-8 precursor [KO:K10030]
282261  IGFBP3; insulin-like growth factor-binding protein 3 precursor [KO:K10138]
281375  SERPINE1; plasminogen activator inhibitor 1 precursor [KO:K03982]
509613  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
788091  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
614773  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
767898  ZFP36L2; zinc finger protein 36, C3H1 type-like 2 [KO:K18753]
408013  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
540259  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
514642  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
281661  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
281662  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
326597  CALM; calmodulin [KO:K02183]
520277  CALM3; calmodulin-3 [KO:K02183]
617095  CALM1; calmodulin-1 [KO:K02183]
520404  CALML5; calmodulin-like protein 5 [KO:K02183]
100297344  CALM2; calmodulin-2 [KO:K02183]
617412  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
104973792  uncharacterized protein LOC104973792 [KO:K02183]
539277  CALML4; calmodulin-like protein 4 [KO:K02183]
286852  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
533527  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
790867  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
282321  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
617585  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
511224  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
530401  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
541127  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
788119  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
317697  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
281878  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
281879  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
282478  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
282479  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
282480  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
541168  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
787122  ADP/ATP translocase 1 [KO:K05863]
132344463  ADP/ATP translocase 3 [KO:K05863]
281420  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
282119  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
282120  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
282716  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
536656  MCU; calcium uniporter protein, mitochondrial precursor [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
bta04020  Calcium signaling pathway
bta04068  FoxO signaling pathway
bta04110  Cell cycle
bta04115  p53 signaling pathway
bta04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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