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

Other DBs
GO: 0090398
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01110  PTEN; 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]
K01367  CAPN1; calpain-1 [EC:3.4.22.52]
K02087  CDK1, CDC2; cyclin-dependent kinase 1 [EC:2.7.11.22 2.7.11.23]
K02089  CDK4; cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  CDK6; cyclin-dependent kinase 6 [EC:2.7.11.22]
K02183  CALM; calmodulin
K02206  CDK2; cyclin-dependent kinase 2 [EC:2.7.11.22]
K02216  CHEK1; serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02678  ETS1, pnt; C-ets-1
K02830  HRAD1, RAD17; cell cycle checkpoint protein [EC:3.1.11.2]
K02833  HRAS; GTPase HRas
K03362  FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K03853  CAPN2; calpain-2 [EC:3.4.22.53]
K03982  SERPINE1, PAI1; plasminogen activator inhibitor 1
K04348  PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04377  MYC; Myc proto-oncogene protein
K04383  IL1A; interleukin 1 alpha
K04388  TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]
K04402  GADD45; growth arrest and DNA-damage-inducible protein
K04432  MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04443  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1]
K04446  NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04451  TP53, P53; tumor protein p53
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04500  SMAD2; mothers against decapentaplegic homolog 2
K04503  CCND1; G1/S-specific cyclin-D1
K04674  TGFBR1, ALK5; TGF-beta receptor type-1 [EC:2.7.11.30]
K04681  RBL1; retinoblastoma-like protein 1
K04682  E2F4_5; transcription factor E2F4/5
K04685  CDKN2B, P15, INK4B; cyclin-dependent kinase inhibitor 2B
K04728  ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]
K04735  RELA; transcription factor p65
K04851  CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04973  TRPV4; transient receptor potential cation channel subfamily V member 4
K04982  TRPM7, CHAK1; transient receptor potential cation channel subfamily M member 7 [EC:2.7.11.1]
K05405  IL6; interleukin 6
K05862  VDAC1; voltage-dependent anion channel protein 1
K05863  SLC25A4S, ANT; solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K05864  PPID, CYPD; peptidyl-prolyl isomerase D [EC:5.2.1.8]
K05868  CCNB1; G2/mitotic-specific cyclin-B1
K06268  PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06269  PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K06618  RB1; retinoblastoma-associated protein
K06620  E2F3; transcription factor E2F3
K06621  CDKN2A, P16, INK4A; cyclin-dependent kinase inhibitor 2A
K06625  CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06626  CCNE; G1/S-specific cyclin-E1
K06627  CCNA; cyclin-A
K06640  ATR; serine/threonine-protein kinase ATR [EC:2.7.11.1]
K06641  CHEK2; serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K06643  MDM2; E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K06645  CDC25A; M-phase inducer phosphatase 1 [EC:3.1.3.48]
K06751  MHC1; MHC class I antigen
K07201  FOXO1; forkhead box protein O1
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07205  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1
K07206  TSC1; tuberous sclerosis 1
K07207  TSC2; tuberous sclerosis 2
K07208  RHEB; Ras homolog enriched in brain
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07829  RRAS; Ras-related protein R-Ras
K07830  RRAS2, TC21; Ras-related protein R-Ras2
K07831  MRAS; Ras-related protein M-Ras
K08015  RASSF5, RAPL; Ras association domain-containing protein 5
K08826  HIPK; homeodomain interacting protein kinase [EC:2.7.11.1]
K09183  GATA4; GATA-binding protein 4
K09389  E2F2; transcription factor E2F2
K09406  FOXM; forkhead box protein M
K09408  FOXO3; forkhead box protein O3
K10030  IL8, CXCL8; interleukin 8
K10138  IGFBP3; insulin-like growth factor-binding protein 3
K10151  CCND2; G1/S-specific cyclin-D2
K10152  CCND3; G1/S-specific cyclin-D3
K10752  RBBP4, HAT2, CAF1, MIS16; histone-binding protein RBBP4
K10865  MRE11; double-strand break repair protein MRE11
K10866  RAD50; DNA repair protein RAD50 [EC:3.6.-.-]
K10867  NBN, NBS1; nibrin
K10903  HUS1; HUS1 checkpoint protein
K10994  RAD9A; cell cycle checkpoint control protein RAD9A [EC:3.1.11.2]
K10995  RAD9B; cell cycle checkpoint control protein RAD9B
K11411  SIRT1, SIR2L1; NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286]
K13375  TGFB1; transforming growth factor beta-1
K13376  TGFB2; transforming growth factor beta-2
K13377  TGFB3; transforming growth factor beta-3
K14381  SQSTM1; sequestosome 1
K15040  VDAC2; voltage-dependent anion channel protein 2
K15041  VDAC3; voltage-dependent anion channel protein 3
K16332  RBL2; retinoblastoma-like protein 2
K17332  NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333  NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17334  NFATC4, NFAT3; nuclear factor of activated T-cells, cytoplasmic 4
K17454  E2F1; transcription factor E2F1
K18753  ZFP36L; butyrate response factor
K20858  MCU; calcium uniporter protein, mitochondrial
K21124  TRAF3IP2, ACT1; adaptor protein CIKS
K21769  MYBL2, B-MYB; myb-related protein B
K21770  CCNB2; G2/mitotic-specific cyclin-B2
K21771  CCNB3; G2/mitotic-specific cyclin-B3
K21773  LIN9; protein lin-9
K21774  LIN37; protein lin-37
K21775  LIN52; protein lin-52
K21776  LIN54; protein lin-54
K23605  SMAD3; mothers against decapentaplegic homolog 3
K24231  KIR2DL4, CD158D; killer cell immunoglobulin-like receptor 2DL4
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
ko04020  Calcium signaling pathway
ko04068  FoxO signaling pathway
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04150  mTOR signaling pathway

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