KEGG   PATHWAY: pale04218
Entry
pale04218                   Pathway                                
Name
Cellular senescence - Pteropus alecto (black flying fox)
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
pale04218  Cellular senescence
pale04218

Other DBs
GO: 0090398
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102884154  TGFB1; transforming growth factor beta-1 [KO:K13375]
102881295  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
102893304  TGFB3; transforming growth factor beta-3 [KO:K13377]
102880759  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
102889618  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
102893928  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102895268  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
102893142  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102896272  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102892640  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102881884  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102890110  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102882545  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102895200  E2F5; transcription factor E2F5 [KO:K04682]
102894891  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102892244  FOXO1; forkhead box protein O1 [KO:K07201]
102890472  FOXO3; forkhead box protein O3 [KO:K09408]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102893397  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102882411  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102882260  CCNE1; LOW QUALITY PROTEIN: G1/S-specific cyclin-E1 [KO:K06626]
102885874  HLA class I histocompatibility antigen, B-48 alpha chain-like [KO:K06751]
102887544  H-2 class I histocompatibility antigen, Q10 alpha chain isoform X2 [KO:K06751]
102898809  LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102881941  RRAS; ras-related protein R-Ras [KO:K07829]
102881508  RRAS2; ras-related protein R-Ras2 [KO:K07830]
102879891  MRAS; ras-related protein M-Ras [KO:K07831]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102878835  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
102898762  TSC2; tuberin isoform X11 [KO:K07207]
102889101  RHEB; GTP-binding protein Rheb [KO:K07208]
102885092  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102881949  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102880351  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
102890664  CCNA1; cyclin-A1 [KO:K06627]
102894080  CCNA2; cyclin-A2 [KO:K06627]
102879195  MYBL2; myb-related protein B [KO:K21769]
102889326  LIN9; protein lin-9 homolog [KO:K21773]
102897155  LIN37; protein lin-37 homolog isoform X2 [KO:K21774]
102886798  LIN52; protein lin-52 homolog isoform X3 [KO:K21775]
102889635  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
102888702  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
102896650  FOXM1; forkhead box protein M1 isoform X6 [KO:K09406]
102895524  MYC; myc proto-oncogene protein [KO:K04377]
102896422  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 2A [KO:K06621]
102884281  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102888616  RASSF5; ras association domain-containing protein 5 isoform X2 [KO:K08015]
102893556  FBXW11; F-box/WD repeat-containing protein 11 isoform X6 [KO:K03362]
102895058  BTRC; F-box/WD repeat-containing protein 1A isoform X3 [KO:K03362]
102878368  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102881006  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
102884013  HIPK1; homeodomain-interacting protein kinase 1 isoform X2 [KO:K08826] [EC:2.7.11.1]
102881116  homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
107195574  homeodomain-interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
102892254  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102881448  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102887827  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102893422  ETS1; protein C-ets-1 [KO:K02678]
102886389  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102888822  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102895900  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888602  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888845  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102877720  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102886440  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102878191  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102885790  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102885939  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102880158  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
102892539  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
102891938  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
102878053  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
102890531  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
102881755  NBN; nibrin isoform X1 [KO:K10867]
102898588  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102882358  CHEK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
102892509  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
102879901  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
102888105  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
102887750  HUS1; checkpoint protein HUS1 isoform X3 [KO:K10903]
102889339  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102882405  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102897196  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
102891735  SQSTM1; LOW QUALITY PROTEIN: sequestosome-1 [KO:K14381]
102882528  GATA4; transcription factor GATA-4 [KO:K09183]
102896596  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
102880692  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102878395  RELA; transcription factor p65 [KO:K04735]
102892998  IL1A; interleukin-1 alpha [KO:K04383]
102895746  IL6; interleukin-6 [KO:K05405]
102892534  CXCL8; interleukin-8 [KO:K10030]
102891216  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
102880028  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
102881655  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102887540  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X4 [KO:K04443] [EC:2.7.11.1]
102878888  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
102887510  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
102888351  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102885612  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102884616  TRPM7; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102891365  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102897695  CAPN2; calpain-2 catalytic subunit isoform X2 [KO:K03853] [EC:3.4.22.53]
102894226  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102897273  CALM3; calmodulin-3 [KO:K02183]
102886058  CALM1; calmodulin-1 [KO:K02183]
102884196  CALML6; calmodulin-like protein 6 [KO:K02183]
102891673  calmodulin-like [KO:K02183]
102893109  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102881744  calmodulin-like [KO:K02183]
102880029  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102883156  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102898473  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102894471  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102895490  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102880857  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102886274  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102884312  NFATC3; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
102888827  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
102894982  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102896356  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102881783  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102897294  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102878001  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102896364  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102896575  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102885895  ADP/ATP translocase 3-like [KO:K05863]
102892937  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
102887036  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102898192  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102892527  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
102896287  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
pale04020  Calcium signaling pathway
pale04068  FoxO signaling pathway
pale04110  Cell cycle
pale04115  p53 signaling pathway
pale04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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