KEGG   PATHWAY: tmu04218
Entry
tmu04218                    Pathway                                
Name
Cellular senescence - Trichechus manatus latirostris (Florida manatee)
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
tmu04218  Cellular senescence
tmu04218

Other DBs
GO: 0090398
Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101342543  transforming growth factor beta-1 isoform X2 [KO:K13375]
101347669  transforming growth factor beta-2 isoform X1 [KO:K13376]
101358028  transforming growth factor beta-3 [KO:K13377]
101359953  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
101354258  TGF-beta receptor type-2 isoform X4 [KO:K04388] [EC:2.7.11.30]
101348656  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101344857  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101351137  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101355276  cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101359745  G1/S-specific cyclin-D1 [KO:K04503]
101351510  G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
101351688  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101355952  retinoblastoma-associated protein isoform X3 [KO:K06618]
101344004  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
101360818  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101357348  transcription factor E2F1 [KO:K17454]
101357556  transcription factor E2F2 [KO:K09389]
101346679  transcription factor E2F3 isoform X1 [KO:K06620]
101352663  transcription factor E2F5 [KO:K04682]
101362006  transcription factor E2F4 isoform X1 [KO:K04682]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101340503  LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
101354741  forkhead box protein O3 [KO:K09408]
101342008  cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101355616  cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
101361662  G1/S-specific cyclin-E2 [KO:K06626]
101344099  G1/S-specific cyclin-E1 [KO:K06626]
101359320  HLA class I histocompatibility antigen, A-80 alpha chain-like [KO:K06751]
101345748  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X3 [KO:K06751]
101346884  HLA class I histocompatibility antigen, A-80 alpha chain-like [KO:K06751]
101347138  HLA class I histocompatibility antigen, B-40 alpha chain-like isoform X1 [KO:K06751]
101345854  class I histocompatibility antigen, Gogo-B*0101 alpha chain-like isoform X1 [KO:K06751]
101350180  patr class I histocompatibility antigen, B-1 alpha chain-like isoform X1 [KO:K06751]
101346109  class I histocompatibility antigen, Gogo-B*0102 alpha chain-like isoform X1 [KO:K06751]
101346365  class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751]
101340887  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
101349740  HLA class I histocompatibility antigen, Cw-12 alpha chain-like [KO:K06751]
101347525  GTPase KRas isoform X3 [KO:K07827]
101344230  GTPase NRas isoform X1 [KO:K07828]
101349553  ras-related protein R-Ras [KO:K07829]
101354889  ras-related protein R-Ras2 [KO:K07830]
101357647  ras-related protein M-Ras isoform X1 [KO:K07831]
101342804  GTPase HRas isoform X2 [KO:K02833]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101347417  hamartin isoform X1 [KO:K07206]
101358131  tuberin [KO:K07207]
101360739  GTP-binding protein Rheb isoform X2 [KO:K07208]
101343808  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101355243  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]
101342951  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
101341432  cyclin-A2 [KO:K06627]
101347141  cyclin-A1 [KO:K06627]
101356933  myb-related protein B isoform X1 [KO:K21769]
101358140  protein lin-9 homolog isoform X1 [KO:K21773]
101347801  protein lin-37 homolog [KO:K21774]
101351826  protein lin-52 homolog isoform X1 [KO:K21775]
101342610  protein lin-54 homolog isoform X5 [KO:K21776]
101355253  histone-binding protein RBBP4 isoform X2 [KO:K10752]
101354349  forkhead box protein M1 isoform X2 [KO:K09406]
101349786  myc proto-oncogene protein [KO:K04377]
101345867  cyclin-dependent kinase inhibitor 2A [KO:K06621]
101349408  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101351852  cellular tumor antigen p53 [KO:K04451]
101344376  ras association domain-containing protein 5 isoform X1 [KO:K08015]
101345935  F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
101354147  F-box/WD repeat-containing protein 11 isoform X2 [KO:K03362]
101358894  homeodomain-interacting protein kinase 3 isoform X4 [KO:K08826] [EC:2.7.11.1]
101346235  homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
101355327  homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
101346326  homeodomain-interacting protein kinase 2 isoform X2 [KO:K08826] [EC:2.7.11.1]
101346316  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101344889  serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
101345455  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101357840  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101343332  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101341078  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101342007  protein C-ets-1 isoform X2 [KO:K02678]
101355711  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
101344286  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101352466  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101347350  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101361614  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101361872  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101353013  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101361119  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101348099  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101344001  cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101347242  G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
101354738  G2/mitotic-specific cyclin-B1-like [KO:K05868]
101346906  G2/mitotic-specific cyclin-B2 [KO:K21770]
101346390  G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
101343371  double-strand break repair protein MRE11 isoform X1 [KO:K10865]
101355635  DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
101346880  nibrin [KO:K10867]
101355206  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
111821652  serine-protein kinase ATM-like [KO:K04728] [EC:2.7.11.1]
101359759  serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
101344240  cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
101346582  cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
101346257  cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
101344590  checkpoint protein HUS1 [KO:K10903]
101341680  serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
101345463  serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
101346532  M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101351010  sequestosome-1 isoform X1 [KO:K14381]
101340315  transcription factor GATA-4 isoform X2 [KO:K09183]
101361676  adapter protein CIKS [KO:K21124]
101351866  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101361706  transcription factor p65 [KO:K04735]
101359155  interleukin-1 alpha isoform X1 [KO:K04383]
101351590  interleukin-6 [KO:K05405]
101358515  interleukin-8 [KO:K10030]
101355131  insulin-like growth factor-binding protein 3 [KO:K10138]
101348466  plasminogen activator inhibitor 1 [KO:K03982]
101361891  eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101342996  MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
101353868  mRNA decay activator protein ZFP36L2 [KO:K18753]
101359426  mRNA decay activator protein ZFP36L1 [KO:K18753]
101357085  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101359728  transient receptor potential cation channel subfamily V member 4 [KO:K04973]
101349029  transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
101341766  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
101341399  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
101347126  calmodulin-2 isoform X2 [KO:K02183]
101361121  LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
101358846  LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]
101346240  calmodulin-3 [KO:K02183]
101358487  calmodulin [KO:K02183]
101346473  calmodulin-like protein 4 [KO:K02183]
101359111  calmodulin-like [KO:K02183]
101353424  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101357894  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101347440  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
101343394  calcineurin subunit B type 1 isoform X2 [KO:K06268]
101355330  calcineurin subunit B type 2 [KO:K06268]
101359059  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101355751  nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332]
101352434  nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101350695  nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
101346534  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101356404  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101354392  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101351885  ADP/ATP translocase 3 [KO:K05863]
101350620  ADP/ATP translocase 4 [KO:K05863]
101341492  ADP/ATP translocase 2 [KO:K05863]
101354695  ADP/ATP translocase 1 [KO:K05863]
101361956  peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
101351096  voltage-dependent anion-selective channel protein 1 [KO:K05862]
101346677  voltage-dependent anion-selective channel protein 2 [KO:K15040]
101351954  voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
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
tmu04020  Calcium signaling pathway
tmu04068  FoxO signaling pathway
tmu04110  Cell cycle
tmu04115  p53 signaling pathway
tmu04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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