KEGG   PATHWAY: pleu04218
Entry
pleu04218                   Pathway                                
Name
Cellular senescence - Peromyscus leucopus (white-footed mouse)
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
pleu04218  Cellular senescence
pleu04218

Other DBs
GO: 0090398
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680760  Tsc2; tuberin isoform X1 [KO:K07207]
114681033  E2f4; transcription factor E2F4 [KO:K04682]
114681035  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
114681336  Trpv4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
114681418  Calm3; calmodulin-3 [KO:K02183]
114681486  Sqstm1; sequestosome-1 [KO:K14381]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114681534  Hipk4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
114681646  Lin37; protein lin-37 homolog [KO:K21774]
114681779  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
114681841  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
114681917  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
114682037  Rbbp4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
114682091  Capn1; LOW QUALITY PROTEIN: calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
114682099  Rela; transcription factor p65 [KO:K04735]
114682640  [KO:K06751]
114682644  [KO:K06751]
114682645  [KO:K06751]
114682649  [KO:K06751]
114682653  [KO:K06751]
114682654  [KO:K06751]
114682655  [KO:K06751]
114682656  [KO:K06751]
114682666  [KO:K06751]
114682671  [KO:K06751]
114682672  [KO:K06751]
114682673  [KO:K06751]
114682677  [KO:K06751]
114682685  [KO:K06751]
114682688  [KO:K06751]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114683205  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
114683255  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114683276  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
114683476  Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
114683953  [KO:K06269] [EC:3.1.3.16]
114684003  Chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
114684032  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
114684418  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
114684433  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
114684772  Hipk1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
114684999  Mre11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
114685127  [KO:K02833]
114685302  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
114685972  [KO:K06641] [EC:2.7.11.1]
114685984  Rad9a; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
114685987  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114686366  [KO:K06751]
114686570  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
114687018  [KO:K06751]
114687019  [KO:K06751]
114687020  [KO:K06751]
114687180  Rras; ras-related protein R-Ras isoform X1 [KO:K07829]
114687933  [KO:K06751]
114687935  [KO:K06751]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114688249  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
114688301  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
114688482  [KO:K06751]
114688488  [KO:K02833]
114688490  [KO:K06751]
114688492  [KO:K06751]
114688512  [KO:K18753]
114688790  [KO:K06751]
114688816  [KO:K06751]
114688817  [KO:K06751]
114688966  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
114689482  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114689756  Il6; interleukin-6 [KO:K05405]
114690277  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
114690458  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
114690630  Lin9; protein lin-9 homolog isoform X1 [KO:K21773]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114690838  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
114690920  [KO:K04674] [EC:2.7.11.30]
114690969  Atr; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114691539  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
114691640  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
114691745  [KO:K04674] [EC:2.7.11.30]
114691762  Lin54; protein lin-54 homolog isoform X2 [KO:K21776]
114691928  [KO:K05862]
114691978  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114692681  Mybl2; myb-related protein B [KO:K21769]
114693019  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114693020  Mapk11; mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
114693171  Tp53; cellular tumor antigen p53 [KO:K04451]
114693314  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
114693493  [KO:K02833]
114693556  Mras; ras-related protein M-Ras isoform X2 [KO:K07831]
114693559  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
114693595  Hras; GTPase HRas isoform X1 [KO:K02833]
114693961  Igfbp3; insulin-like growth factor-binding protein 3 [KO:K10138]
114694445  [KO:K05863]
114694498  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
114694542  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
114694576  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
114694600  Nbn; nibrin isoform X1 [KO:K10867]
114694883  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
114694913  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
114695335  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114695858  Foxo1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
114695883  Ccna1; cyclin-A1 [KO:K06627]
114696284  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
114696553  [KO:K02833]
114696885  Traf3ip2; LOW QUALITY PROTEIN: E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
114697224  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
114697601  Rras2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
114697780  Zfp36l1; mRNA decay activator protein ZFP36L1 [KO:K18753]
114697904  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
114698053  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
114698056  Rassf5; LOW QUALITY PROTEIN: ras association domain-containing protein 5 [KO:K08015]
114698210  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
114698222  Lin52; protein lin-52 homolog isoform X1 [KO:K21775]
114698354  [KO:K04685]
114698355  [KO:K06621]
114698532  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
114698582  Nras; GTPase NRas [KO:K07828]
114698768  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
114698792  Rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
114698806  [KO:K04348] [EC:3.1.3.16]
114698889  Ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
114698992  Hipk3; homeodomain-interacting protein kinase 3 isoform X3 [KO:K08826] [EC:2.7.11.1]
114699780  Ets1; protein C-ets-1 isoform X1 [KO:K02678]
114700070  Rheb; GTP-binding protein Rheb [KO:K07208]
114700198  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114700220  Vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
114700482  Ppid; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
114700921  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
114701050  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
114701128  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
114701179  Slc25a4; ADP/ATP translocase 1 [KO:K05863]
114701429  Foxm1; forkhead box protein M1 isoform X2 [KO:K09406]
114701440  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
114701991  Myc; myc proto-oncogene protein [KO:K04377]
114702344  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
114702777  Tsc1; hamartin isoform X1 [KO:K07206]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114703361  [KO:K09183]
114703850  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114703855  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
114704095  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114704566  Rad9b; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
114704570  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
114704814  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114704977  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
114705020  Calm1; calmodulin-1 [KO:K02183]
114705236  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
114705331  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
114705416  Slc25a5; ADP/ATP translocase 2 [KO:K05863]
114705519  Ppp3r1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
114705743  Vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
114705846  [KO:K06751]
114706123  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114706157  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
114706162  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114706165  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114706553  E2f1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
114706812  Hipk2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
114706924  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114707180  Ccna2; cyclin-A2 [KO:K06627]
114707244  [KO:K21769]
114707517  Foxo3; LOW QUALITY PROTEIN: forkhead box protein O3 [KO:K09408]
114708031  Hus1; checkpoint protein HUS1 isoform X1 [KO:K10903]
114708125  Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
114708260  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
114708393  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114708477  Kras; GTPase KRas isoform X2 [KO:K07827]
114708726  Nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
114708768  [KO:K02183]
114708779  Calml3; calmodulin-like protein 3 [KO:K02183]
114708890  Mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
114708955  Zfp36l2; mRNA decay activator protein ZFP36L2 isoform X1 [KO:K18753]
114709085  Trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
114709209  Calm2; calmodulin-2 [KO:K02183]
114709525  Il1a; interleukin-1 alpha [KO:K04383]
114709670  Mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114709997  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
114710323  Serpine1; plasminogen activator inhibitor 1 [KO:K03982]
114710523  [KO:K04371] [EC:2.7.11.24]
114710781  Slc25a31; ADP/ATP translocase 4 [KO:K05863]
114710789  Rad1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
114711016  [KO:K05863]
119086118  [KO:K09183]
119089216  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
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
pleu04020  Calcium signaling pathway
pleu04068  FoxO signaling pathway
pleu04110  Cell cycle
pleu04115  p53 signaling pathway
pleu04150  mTOR signaling pathway
KO pathway
ko04218   

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