KEGG   PATHWAY: hhv04218
Entry
hhv04218                    Pathway                                
Name
Cellular senescence - Hyaena hyaena (striped hyena)
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
hhv04218  Cellular senescence
hhv04218

Other DBs
GO: 0090398
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120243258  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
120221741  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
120231992  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
120233513  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
120224680  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
120229672  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120221278  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120223236  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
120248012  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
120247482  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120233874  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120247732  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
120238692  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120220837  RB1; retinoblastoma-associated protein [KO:K06618]
120228633  RBL1; retinoblastoma-like protein 1 [KO:K04681]
120237907  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
120242807  E2F1; transcription factor E2F1 [KO:K17454]
120232903  E2F2; transcription factor E2F2 [KO:K09389]
120235248  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
120224881  E2F4; transcription factor E2F4 [KO:K04682]
120246140  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
120233608  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120220979  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120246696  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120219997  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120239233  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120247089  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
120234298  FOXO1; forkhead box protein O1 [KO:K07201]
120235194  FOXO3; forkhead box protein O3 [KO:K09408]
120233834  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
120219963  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
120219657  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
120231725  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
120226363  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
120221878  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
120221918  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
120222660  class I histocompatibility antigen, Gogo-B*0101 alpha chain-like [KO:K06751]
120223531  KRAS; GTPase KRas [KO:K07827]
120243068  NRAS; GTPase NRas [KO:K07828]
120244187  RRAS; ras-related protein R-Ras [KO:K07829]
120244997  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
120222404  MRAS; ras-related protein M-Ras [KO:K07831]
120223392  HRAS; GTPase HRas isoform X1 [KO:K02833]
120235277  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120244696  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120247774  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120230192  TSC1; hamartin isoform X1 [KO:K07206]
120241477  TSC2; tuberin isoform X1 [KO:K07207]
120230931  RHEB; GTP-binding protein Rheb [KO:K07208]
120233604  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
120235953  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]
120232500  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
120238030  CCNA2; cyclin-A2 [KO:K06627]
120245010  CCNA1; cyclin-A1 [KO:K06627]
120242622  MYBL2; myb-related protein B isoform X1 [KO:K21769]
120234164  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
120243491  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
120231981  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
120246461  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
120231926  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
120234455  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
120240874  MYC; myc proto-oncogene protein [KO:K04377]
120223233  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
120234269  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
120240795  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
120231386  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
120228927  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
120243193  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
120234082  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
120243063  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
120232545  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
120232951  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
120242272  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
120233909  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120239251  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
120235890  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
120231327  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120221655  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120242086  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
120238830  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120242212  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
120237105  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
120228759  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
120230246  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
120233796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120233829  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120234701  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120235253  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
120232638  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120237943  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120242325  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120244139  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
120247955  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
120230878  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
120223135  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
120247190  MRE11; double-strand break repair protein MRE11 [KO:K10865]
120245480  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
120237337  NBN; nibrin isoform X1 [KO:K10867]
120229863  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
120227007  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
120233907  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
120241864  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
120242467  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
120234052  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
120221751  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
120243919  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
120229362  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
120245681  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
120222033  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
120245255  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
120222817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
120240185  RELA; transcription factor p65 [KO:K04735]
120231610  IL1A; interleukin-1 alpha [KO:K04383]
120236228  IL6; interleukin-6 isoform X1 [KO:K05405]
120231052  CXCL8; interleukin-8 [KO:K10030]
120238887  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
120239343  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
120238652  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
120245595  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:2.7.11.1]
120232043  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
120237425  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
120239388  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
120242221  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
120235011  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
120240133  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
120234148  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
120232098  CALM1; calmodulin-1 [KO:K02183]
120237182  calmodulin-like [KO:K02183]
120237195  calmodulin-like protein 3 [KO:K02183]
120241014  CALM2; calmodulin-2 [KO:K02183]
120221982  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
120241987  CALM3; calmodulin-3 isoform X1 [KO:K02183]
120242524  CALML6; calmodulin-like protein 6 [KO:K02183]
120225617  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
120233735  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120239494  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120220964  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120236651  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120240942  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
120230427  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
120223543  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
120247040  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
120237135  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
120237482  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
120238181  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
120240573  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
120222124  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
120246386  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
120248075  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
120248500  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
120238512  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
120233718  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
120234907  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2-like [KO:K15040]
120234009  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
120233756  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
hhv04020  Calcium signaling pathway
hhv04068  FoxO signaling pathway
hhv04110  Cell cycle
hhv04115  p53 signaling pathway
hhv04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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