KEGG   PATHWAY: gas04218
Entry
gas04218                    Pathway                                
Name
Cellular senescence - Gracilinanus agilis (agile gracile opossum)
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
gas04218  Cellular senescence
gas04218

Other DBs
GO: 0090398
Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123230745  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
123230824  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
123230857  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123231024  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
123231037  TSC2; tuberin [KO:K07207]
123231247  [KO:K04685]
123231248  [KO:K04685]
123231518  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
123232226  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123232355  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
123232515  [KO:K07828]
123232936  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
123232952  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
123232957  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
123233053  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]
123233108  [KO:K06751]
123233110  [KO:K06751]
123233132  [KO:K06751]
123233133  [KO:K06751]
123233134  [KO:K06751]
123233185  [KO:K06627]
123233186  [KO:K06627]
123233190  [KO:K06627]
123233191  [KO:K06627]
123233359  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
123233796  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
123234111  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
123234414  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
123234493  [KO:K06751]
123234494  [KO:K06751]
123234496  [KO:K06751]
123234499  [KO:K06751]
123234537  [KO:K21775]
123234651  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
123235210  TSC1; hamartin isoform X1 [KO:K07206]
123235321  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123235446  MYBL2; myb-related protein B isoform X1 [KO:K21769]
123235468  E2F1; transcription factor E2F1 [KO:K17454]
123235863  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123236114  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
123236129  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123236271  IL1A; interleukin-1 alpha [KO:K04383]
123236533  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
123236785  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
123236850  CALM2; calmodulin-2 [KO:K02183]
123236876  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123236954  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
123236979  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
123236992  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
123237004  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
123237064  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123237139  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
123237309  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
123237411  RBL1; retinoblastoma-like protein 1 [KO:K04681]
123237461  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
123237495  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
123237620  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123237627  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
123237635  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
123237719  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
123237729  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
123237797  LIN52; protein lin-52 homolog [KO:K21775]
123237842  CALM1; calmodulin-1 isoform X1 [KO:K02183]
123237945  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
123238038  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
123238040  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
123238130  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
123238314  E2F5; transcription factor E2F5 [KO:K04682]
123238925  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
123239466  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123239917  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
123240067  E2F3; transcription factor E2F3 [KO:K06620]
123240288  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123240305  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123240431  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
123240551  RB1; retinoblastoma-associated protein [KO:K06618]
123240633  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
123240646  NBN; nibrin isoform X1 [KO:K10867]
123240740  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
123240765  [KO:K06627]
123241253  FOXO1; forkhead box protein O1 [KO:K07201]
123241261  CCNA1; cyclin-A1 [KO:K06627]
123241332  MRE11; double-strand break repair protein MRE11 [KO:K10865]
123241475  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
123241522  MRAS; ras-related protein M-Ras [KO:K07831]
123241543  MYC; myc proto-oncogene protein [KO:K04377]
123241957  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
123242322  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123242560  [KO:K02183]
123242567  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
123242831  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123242998  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123243007  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123243054  CALML6; calmodulin-like protein 6 [KO:K02183]
123243677  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
123243714  [KO:K06751]
123243797  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
123243800  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123243860  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123243948  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
123244092  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
123244336  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
123244534  TP53; cellular tumor antigen p53 [KO:K04451]
123244865  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123245045  SERPINE1; plasminogen activator inhibitor 1 isoform X1 [KO:K03982]
123245212  [KO:K06751]
123245214  [KO:K06751]
123245219  [KO:K06751]
123245256  [KO:K04973]
123245414  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123245608  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123245714  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
123246222  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
123246364  [KO:K06751]
123246373  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
123246566  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
123246605  [KO:K06626]
123246606  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
123247136  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
123247194  NRAS; GTPase NRas [KO:K07828]
123247425  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123247441  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:2.7.11.1]
123247693  FOXO3; forkhead box protein O3 [KO:K09408]
123247856  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
123248452  RHEB; GTP-binding protein Rheb [KO:K07208]
123248655  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123248684  KRAS; GTPase KRas isoform X1 [KO:K07827]
123248749  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
123248961  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123249391  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
123249650  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
123249688  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123250011  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123250493  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
123250523  [KO:K02183]
123250672  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
123250729  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123251065  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123251115  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
123251123  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
123251269  RAD9A; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
123251284  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123251290  RELA; transcription factor p65 isoform X1 [KO:K04735]
123251651  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
123251663  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
123251689  CCNA2; cyclin-A2 [KO:K06627]
123251756  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
123251828  [KO:K07827]
123251829  [KO:K06643] [EC:2.3.2.27]
123251985  [KO:K06626]
123252071  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
123252152  [KO:K10030]
123252171  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
123252235  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
123252239  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
123252806  [KO:K06269] [EC:3.1.3.16]
123252907  RRAS2; ras-related protein R-Ras2 [KO:K07830]
123253831  [KO:K06751]
123253834  [KO:K06751]
123254538  RRAS; ras-related protein R-Ras isoform X1 [KO:K07829]
123254835  LIN37; protein lin-37 homolog [KO:K21774]
123255152  IL6; interleukin-6 [KO:K05405]
123255254  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
123255734  [KO:K06751]
123255768  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
123256028  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123256513  [KO:K02649]
123256515  [KO:K02649]
123256534  [KO:K02183]
123256535  [KO:K02183]
123256600  [KO:K08826] [EC:2.7.11.1]
123256609  [KO:K08826] [EC:2.7.11.1]
123256922  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
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
gas04020  Calcium signaling pathway
gas04068  FoxO signaling pathway
gas04110  Cell cycle
gas04115  p53 signaling pathway
gas04150  mTOR signaling pathway
KO pathway
ko04218   

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