KEGG   PATHWAY: ko04218
Entry
ko04218                     Pathway                                

Name
Cellular senescence
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
ko04218  Cellular senescence
ko04218

Disease
H00064  Ataxia telangiectasia
Other DBs
GO: 0090398
Orthology
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K04674  TGF-beta receptor type-1 [EC:2.7.11.30]
K04388  TGF-beta receptor type-2 [EC:2.7.11.30]
K04500  mothers against decapentaplegic homolog 2
K23605  mothers against decapentaplegic homolog 3
K04685  cyclin-dependent kinase inhibitor 2B
K02089  cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  cyclin-dependent kinase 6 [EC:2.7.11.22]
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K06618  retinoblastoma-associated protein
K04681  retinoblastoma-like protein 1
K16332  retinoblastoma-like protein 2
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K04682  transcription factor E2F4/5
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K07201  forkhead box protein O1
K09408  forkhead box protein O3
K06625  cyclin-dependent kinase inhibitor 1A
K02206  cyclin-dependent kinase 2 [EC:2.7.11.22]
K06626  G1/S-specific cyclin-E1
K06751  MHC class I antigen
K24231  killer cell immunoglobulin-like receptor 2DL4
K07827  GTPase KRas
K07828  GTPase NRas
K07829  Ras-related protein R-Ras
K07830  Ras-related protein R-Ras2
K07831  Ras-related protein M-Ras
K02833  GTPase HRas
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K07206  tuberous sclerosis 1
K07207  tuberous sclerosis 2
K07208  Ras homolog enriched in brain
K07203  serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K11411  NAD+-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286]
K06627  cyclin-A
K21769  myb-related protein B
K21773  protein lin-9
K21774  protein lin-37
K21775  protein lin-52
K21776  protein lin-54
K10752  histone-binding protein RBBP4
K09406  forkhead box protein M
K04377  Myc proto-oncogene protein
K06621  cyclin-dependent kinase inhibitor 2A
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K04451  tumor protein p53
K08015  Ras association domain-containing protein 5
K03362  F-box and WD-40 domain protein 1/11
K08826  homeodomain interacting protein kinase [EC:2.7.11.1]
K06269  serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K02678  C-ets-1
K04432  mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04402  growth arrest and DNA-damage-inducible protein
K02087  cyclin-dependent kinase 1 [EC:2.7.11.22 2.7.11.23]
K05868  G2/mitotic-specific cyclin-B1
K21770  G2/mitotic-specific cyclin-B2
K21771  G2/mitotic-specific cyclin-B3
K10865  double-strand break repair protein MRE11
K10866  DNA repair protein RAD50 [EC:3.6.-.-]
K10867  nibrin
K04728  serine-protein kinase ATM [EC:2.7.11.1]
K06641  serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K10994  cell cycle checkpoint control protein RAD9A [EC:3.1.11.2]
K10995  cell cycle checkpoint control protein RAD9B
K02830  cell cycle checkpoint protein [EC:3.1.11.2]
K10903  HUS1 checkpoint protein
K06640  serine/threonine-protein kinase ATR [EC:2.7.11.1]
K02216  serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K06645  M-phase inducer phosphatase 1 [EC:3.1.3.48]
K14381  sequestosome 1
K09183  GATA-binding protein 4
K21124  adaptor protein CIKS
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04383  interleukin 1 alpha
K05405  interleukin 6
K10030  interleukin 8
K10138  insulin-like growth factor-binding protein 3
K03982  plasminogen activator inhibitor 1
K07205  eukaryotic translation initiation factor 4E binding protein 1
K04443  mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1]
K18753  butyrate response factor
K04851  voltage-dependent calcium channel L type alpha-1D
K04973  transient receptor potential cation channel subfamily V member 4
K04982  transient receptor potential cation channel subfamily M member 7 [EC:2.7.11.1]
K01367  calpain-1 [EC:3.4.22.52]
K03853  calpain-2 [EC:3.4.22.53]
K02183  calmodulin
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K17333  nuclear factor of activated T-cells, cytoplasmic 3
K17334  nuclear factor of activated T-cells, cytoplasmic 4
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K05863  solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K05864  peptidyl-prolyl isomerase D [EC:5.2.1.8]
K05862  voltage-dependent anion channel protein 1
K15040  voltage-dependent anion channel protein 2
K15041  voltage-dependent anion channel protein 3
K20858  calcium uniporter protein, mitochondrial
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07909  Sirolimus
C16844  Hydroxyl radical
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
ko04020  Calcium signaling pathway
ko04068  FoxO signaling pathway
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04150  mTOR signaling pathway
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