KEGG   PATHWAY: cfr04218
Entry
cfr04218                    Pathway                                
Name
Cellular senescence - Camelus ferus (Wild Bactrian camel)
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
cfr04218  Cellular senescence
cfr04218

Other DBs
GO: 0090398
Organism
Camelus ferus (Wild Bactrian camel) [GN:cfr]
Gene
102509937  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
102505811  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102517948  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
102522485  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
102509744  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
102508588  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102523073  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
116663067  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102522300  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102520456  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102518309  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
116661359  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102524562  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102516870  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102509030  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102524019  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102517851  E2F1; transcription factor E2F1 [KO:K17454]
102515523  E2F2; transcription factor E2F2 [KO:K09389]
102513737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102517931  E2F4; transcription factor E2F4 [KO:K04682]
102507844  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
102523502  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102518643  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102519994  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102513205  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102505690  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102520923  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102511562  FOXO1; forkhead box protein O1 isoform X1 [KO:K07201]
102513603  FOXO3; LOW QUALITY PROTEIN: forkhead box protein O3 [KO:K09408]
102509404  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
102504649  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102516466  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
102512815  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102504730  patr class I histocompatibility antigen, B-1 alpha chain isoform X1 [KO:K06751]
102507402  H-2 class I histocompatibility antigen, Q10 alpha chain [KO:K06751]
102508006  BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X1 [KO:K06751]
102516242  HLA class I histocompatibility antigen, B alpha chain-like isoform X1 [KO:K06751]
102517613  patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751]
106730534  saoe class I histocompatibility antigen, A alpha chain-like isoform X1 [KO:K06751]
116658362  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
116658363  LOW QUALITY PROTEIN: class I histocompatibility antigen, Gogo-B*0102 alpha chain-like [KO:K06751]
102516372  KRAS; GTPase KRas isoform X1 [KO:K07827]
102509562  NRAS; GTPase NRas [KO:K07828]
102517735  RRAS; ras-related protein R-Ras [KO:K07829]
102522438  RRAS2; ras-related protein R-Ras2 [KO:K07830]
102518807  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
102524334  HRAS; GTPase HRas isoform X1 [KO:K02833]
102503460  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102515350  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102519101  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
106729149  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102504505  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
102523349  TSC2; tuberin isoform X1 [KO:K07207]
102508479  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
102510836  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
102515104  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]
102515768  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X2 [KO:K11411] [EC:2.3.1.286]
102513162  CCNA2; cyclin-A2 [KO:K06627]
102517118  CCNA1; cyclin-A1 [KO:K06627]
102515994  MYBL2; myb-related protein B isoform X1 [KO:K21769]
102517559  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
102507535  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
102523753  LIN52; protein lin-52 homolog isoform X2 [KO:K21775]
102515973  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
102509796  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
102505998  histone-binding protein RBBP4 [KO:K10752]
102519368  FOXM1; LOW QUALITY PROTEIN: forkhead box protein M1 [KO:K09406]
102511086  MYC; myc proto-oncogene protein [KO:K04377]
102517211  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
102522420  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102524476  TP53; cellular tumor antigen p53 [KO:K04451]
102519008  RASSF5; ras association domain-containing protein 5 isoform X2 [KO:K08015]
102509669  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
102521888  FBXW11; F-box/WD repeat-containing protein 11 isoform X5 [KO:K03362]
102508667  HIPK4; LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102512371  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
102507222  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
102505271  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
102522874  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
102520782  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102505354  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102517521  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102515937  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102511209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102517586  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102521659  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102520999  ETS1; protein C-ets-1 isoform X5 [KO:K02678]
102523780  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102519784  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102516847  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102519781  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102511298  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102511078  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102516207  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102508482  GADD45A; LOW QUALITY PROTEIN: growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116660720  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102511381  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102522147  CCNB1; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1 [KO:K05868]
102523319  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102521221  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
102515571  MRE11; LOW QUALITY PROTEIN: double-strand break repair protein MRE11 [KO:K10865]
102522123  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
102506568  NBN; LOW QUALITY PROTEIN: nibrin [KO:K10867]
102511995  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102508820  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
102520642  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
102508669  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
102515412  RAD1; cell cycle checkpoint protein RAD1 isoform X1 [KO:K02830] [EC:3.1.11.2]
102513952  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
102516904  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102505566  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102509600  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
102519914  SQSTM1; sequestosome-1 [KO:K14381]
102523441  GATA4; LOW QUALITY PROTEIN: transcription factor GATA-4 [KO:K09183]
102507269  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
102505905  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102506204  RELA; transcription factor p65 isoform X1 [KO:K04735]
102521743  IL1A; interleukin-1 alpha [KO:K04383]
102515320  IL6; interleukin-6 [KO:K05405]
102506409  CXCL8; interleukin-8 [KO:K10030]
102520723  IGFBP3; insulin-like growth factor-binding protein 3 isoform X1 [KO:K10138]
102505188  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
102520195  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102508766  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102515790  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
116668963  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
102504854  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102515574  TRPV4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102518266  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102517688  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102512386  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102512690  CALM1; calmodulin-1 [KO:K02183]
102516816  CALM3; calmodulin-3 [KO:K02183]
102509134  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
102517946  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102512134  CALM2; calmodulin-2 [KO:K02183]
102518712  calmodulin [KO:K02183]
102513924  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102515660  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102505131  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
106729683  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
116669020  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102523589  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102521501  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102514634  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102506833  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
102521814  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102517295  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102524078  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102503644  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102513318  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102516285  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102512378  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102520419  LOW QUALITY PROTEIN: ADP/ATP translocase 2-like [KO:K05863]
102510841  PPID; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
102518825  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
116669325  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102520541  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
106730896  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2-like [KO:K15040]
102509027  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
102507581  MCU; calcium uniporter protein, mitochondrial isoform X1 [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
cfr04020  Calcium signaling pathway
cfr04068  FoxO signaling pathway
cfr04110  Cell cycle
cfr04115  p53 signaling pathway
cfr04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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