KEGG   PATHWAY: uar04218
Entry
uar04218                    Pathway                                
Name
Cellular senescence - Ursus americanus (American black bear)
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
uar04218  Cellular senescence
uar04218

Other DBs
GO: 0090398
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123781846  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
123800112  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123798962  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123781069  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
123777686  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123787367  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
123800821  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
123781261  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
123787201  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123789288  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
123778441  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
123781570  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123779180  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123791847  RB1; retinoblastoma-associated protein [KO:K06618]
123796962  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
123798407  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
123798360  E2F1; transcription factor E2F1 [KO:K17454]
123782351  E2F2; transcription factor E2F2 [KO:K09389]
123791040  E2F3; LOW QUALITY PROTEIN: transcription factor E2F3 [KO:K06620]
123803510  E2F4; transcription factor E2F4 [KO:K04682]
123797922  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
123786407  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123788422  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123779078  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123800228  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123793748  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
123779926  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123791891  FOXO1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
123798497  FOXO3; forkhead box protein O3 [KO:K09408]
123779575  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123787272  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123797872  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
123791375  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123785045  class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751]
123793445  HLA class I histocompatibility antigen, B alpha chain-like [KO:K06751]
123794160  uncharacterized protein LOC123794160 [KO:K06751]
123780238  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
123791023  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
123791025  LOW QUALITY PROTEIN: class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751]
123791026  DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]
123791029  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
123801699  KRAS; GTPase KRas isoform X1 [KO:K07827]
123795037  NRAS; GTPase NRas [KO:K07828]
123776255  RRAS; ras-related protein R-Ras isoform X1 [KO:K07829]
123791661  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
123788418  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
123775506  HRAS; GTPase HRas isoform X1 [KO:K02833]
123793473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123784096  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123791373  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123775611  TSC1; hamartin isoform X1 [KO:K07206]
123783731  TSC2; tuberin isoform X1 [KO:K07207]
123788761  RHEB; GTP-binding protein Rheb [KO:K07208]
123779112  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123795550  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]
123782872  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
123793313  CCNA2; cyclin-A2 [KO:K06627]
123791767  CCNA1; cyclin-A1 [KO:K06627]
123797007  MYBL2; myb-related protein B isoform X1 [KO:K21769]
123791735  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
123793896  LIN37; protein lin-37 homolog [KO:K21774]
123798998  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
123787746  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
123782197  RBBP4; histone-binding protein RBBP4 [KO:K10752]
123781632  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
123801908  MYC; myc proto-oncogene protein [KO:K04377]
123781143  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
123787146  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
123792132  TP53; cellular tumor antigen p53 [KO:K04451]
123785660  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
123788591  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
123795885  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
123795043  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
123788886  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
123784049  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
123799439  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
123799882  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123795174  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123778467  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
123779126  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123802053  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123800861  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123796818  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123795639  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123784602  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123783200  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
123779716  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
123803240  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
123803776  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123803793  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
123776209  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123776212  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123793985  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123795328  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
123776460  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123783025  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
123800258  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
123784090  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
123785057  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
123787853  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
123790367  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
123797902  NBN; nibrin isoform X1 [KO:K10867]
123792533  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
123788135  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
123778466  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
123779164  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
123785466  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
123789485  HUS1; checkpoint protein HUS1 [KO:K10903]
123788444  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
123792711  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
123779966  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
123790491  SQSTM1; sequestosome-1 [KO:K14381]
123793541  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
123792960  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
123788912  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123778302  RELA; transcription factor p65 [KO:K04735]
123799742  IL1A; interleukin-1 alpha [KO:K04383]
123788681  IL6; interleukin-6 [KO:K05405]
123789115  CXCL8; interleukin-8 [KO:K10030]
123789482  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
123777298  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
123780411  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
123785786  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
123799051  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
123776027  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
123798762  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
123788209  TRPV4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
123801864  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
123778287  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
123791973  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
123785908  CALM2; calmodulin-2 [KO:K02183]
123800842  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123802291  calmodulin-like [KO:K02183]
123802321  CALML3; calmodulin-like protein 3 [KO:K02183]
123796079  CALML6; calmodulin-like protein 6 [KO:K02183]
123798898  CALM1; calmodulin-1 [KO:K02183]
123778741  CALM3; calmodulin-3 [KO:K02183]
123788880  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123782828  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123777460  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123786008  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
123781022  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
123787495  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
123799385  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
123803502  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
123795735  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
123799165  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123801684  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123790908  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
123793297  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
123787795  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
123802759  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
123784508  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
123793182  PPID; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
123790351  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
123788811  voltage-dependent anion-selective channel protein 2 [KO:K15040]
123782868  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
123780315  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
123782996  MCU; calcium uniporter protein, mitochondrial [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
uar04020  Calcium signaling pathway
uar04068  FoxO signaling pathway
uar04110  Cell cycle
uar04115  p53 signaling pathway
uar04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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