KEGG   PATHWAY: umr04218
Entry
umr04218                    Pathway                                
Name
Cellular senescence - Ursus maritimus (polar bear)
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
umr04218  Cellular senescence
umr04218

Other DBs
GO: 0090398
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656357  [KO:K06751]
103656694  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103656869  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
103656991  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
103657130  RRAS; ras-related protein R-Ras isoform X2 [KO:K07829]
103657204  CALM3; calmodulin-3 [KO:K02183]
103657756  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103658066  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
103658194  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103658473  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
103658475  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103658796  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103658871  IL6; interleukin-6 [KO:K05405]
103659121  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
103659236  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
103659338  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
103660368  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103660629  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
103660663  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
103660707  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
103660943  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661095  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
103661178  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
103661277  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103661328  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
103661444  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103661461  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
103661472  NBN; nibrin isoform X1 [KO:K10867]
103661697  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103661798  CCNA2; cyclin-A2 [KO:K06627]
103661921  [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103662311  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
103662421  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
103663135  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
103663314  [KO:K04402]
103663615  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103663818  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
103663834  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
103663939  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103664092  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
103664372  CCNA1; cyclin-A1 [KO:K06627]
103664495  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
103664724  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
103665244  KRAS; GTPase KRas isoform X1 [KO:K07827]
103665275  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103665307  CXCL8; interleukin-8 [KO:K10030]
103665362  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665536  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103665553  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103665687  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103666331  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
103666434  RBBP4; histone-binding protein RBBP4 [KO:K10752]
103666660  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103666789  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103666989  [KO:K06621]
103667094  LIN9; protein lin-9 homolog isoform X4 [KO:K21773]
103667741  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103667762  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X2 [KO:K11411] [EC:2.3.1.286]
103667825  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103667846  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
103668021  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
103668779  TSC2; tuberin isoform X1 [KO:K07207]
103669038  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
103669131  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103669173  [KO:K02833]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103669422  NRAS; GTPase NRas [KO:K07828]
103669457  HIPK1; homeodomain-interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103669597  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103669778  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103669832  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103669885  MYBL2; myb-related protein B isoform X1 [KO:K21769]
103670125  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
103670250  TSC1; hamartin [KO:K07206]
103670304  CALM1; calmodulin-1 isoform X1 [KO:K02183]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103670922  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103671019  RASSF5; LOW QUALITY PROTEIN: ras association domain-containing protein 5 [KO:K08015]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103671139  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103671210  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
103671240  CALM2; calmodulin-2 [KO:K02183]
103671340  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
103671715  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
103671864  IL1A; interleukin-1 alpha [KO:K04383]
103671909  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103672268  [KO:K06751]
103673318  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103673668  E2F4; transcription factor E2F4 [KO:K04682]
103673717  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
103673796  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103674455  E2F1; transcription factor E2F1 [KO:K17454]
103674670  HUS1; checkpoint protein HUS1 [KO:K10903]
103674673  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
103674739  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103675112  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103675729  FOXM1; forkhead box protein M1 [KO:K09406]
103675743  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103675835  FOXO3; forkhead box protein O3 [KO:K09408]
103675980  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103676238  [KO:K02183]
103676239  CALML3; calmodulin-like protein 3 [KO:K02183]
103676738  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103676798  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103676992  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
103677056  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
103677394  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
103677688  RB1; retinoblastoma-associated protein [KO:K06618]
103677704  FOXO1; forkhead box protein O1 [KO:K07201]
103677737  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
103677943  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103678292  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
103678381  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
103678383  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
103678534  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103678627  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
103678665  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
103678776  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
103679049  CALML4; calmodulin-like protein 4 isoform X3 [KO:K02183]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103679154  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103679332  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
103679450  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
103679584  RELA; transcription factor p65 [KO:K04735]
103679610  RAD9A; cell cycle checkpoint control protein RAD9A isoform X3 [KO:K10994] [EC:3.1.11.2]
103679611  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
103679831  [KO:K04685]
103680014  SQSTM1; sequestosome-1 [KO:K14381]
103680441  [KO:K06751]
103680561  [KO:K06751]
103681007  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
103681651  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103682015  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
103682041  CALML6; calmodulin-like protein 6 [KO:K02183]
103682344  [KO:K06751]
103682372  RRAS2; LOW QUALITY PROTEIN: ras-related protein R-Ras2 [KO:K07830]
103682503  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
103682518  LIN37; protein lin-37 homolog [KO:K21774]
121100135  [KO:K04402]
121101050  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
121104340  [KO:K06751]
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
umr04020  Calcium signaling pathway
umr04068  FoxO signaling pathway
umr04110  Cell cycle
umr04115  p53 signaling pathway
umr04150  mTOR signaling pathway
KO pathway
ko04218   

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