KEGG   PATHWAY: mun04218
Entry
mun04218                    Pathway                                
Name
Cellular senescence - Meriones unguiculatus (Mongolian gerbil)
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
mun04218  Cellular senescence
mun04218

Other DBs
GO: 0090398
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110561197  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110549244  Tgfb2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
110558214  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
110551136  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110547249  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110550301  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110557887  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110554385  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
110561245  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
110558380  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
110546940  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
110548628  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110550225  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
110553592  Rb1; retinoblastoma-associated protein [KO:K06618]
110566281  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
110548204  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
110554547  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110545385  E2f2; transcription factor E2F2 [KO:K09389]
110561800  E2f3; transcription factor E2F3 isoform X3 [KO:K06620]
110545636  E2f4; transcription factor E2F4 isoform X1 [KO:K04682]
110563235  E2f5; transcription factor E2F5 [KO:K04682]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110549421  Foxo1; forkhead box protein O1 [KO:K07201]
110555699  Foxo3; forkhead box protein O3 [KO:K09408]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110559398  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110545702  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110561277  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110557144  H-2 class I histocompatibility antigen, D-37 alpha chain-like [KO:K06751]
110557146  RT1 class I histocompatibility antigen, AA alpha chain-like isoform X1 [KO:K06751]
110562341  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X3 [KO:K06751]
110563045  patr class I histocompatibility antigen, A-126 alpha chain-like [KO:K06751]
110563046  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
110563052  class I histocompatibility antigen, B alpha chain-like [KO:K06751]
110543171  H-2 class I histocompatibility antigen, K-D alpha chain-like [KO:K06751]
110543428  RT1 class I histocompatibility antigen, AA alpha chain-like isoform X1 [KO:K06751]
110544579  patr class I histocompatibility antigen, A-126 alpha chain-like [KO:K06751]
132648276  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
110543095  RT1 class I histocompatibility antigen, AA alpha chain-like isoform X1 [KO:K06751]
110557135  RT1 class I histocompatibility antigen, AA alpha chain [KO:K06751]
132648299  RT1 class I histocompatibility antigen, AA alpha chain-like isoform X1 [KO:K06751]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110544642  GTPase NRas [KO:K07828]
110544765  Nras; GTPase NRas [KO:K07828]
110546864  Rras; ras-related protein R-Ras isoform X1 [KO:K07829]
110556050  Rras2; ras-related protein R-Ras2 [KO:K07830]
110548400  Mras; ras-related protein M-Ras [KO:K07831]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110550703  Tsc1; hamartin isoform X1 [KO:K07206]
110553023  Tsc2; tuberin isoform X1 [KO:K07207]
110565714  Rheb; GTP-binding protein Rheb [KO:K07208]
110548161  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110561175  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]
110554873  Sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
110559633  Ccna2; cyclin-A2 isoform X1 [KO:K06627]
110554919  Ccna1; cyclin-A1 [KO:K06627]
110548232  Mybl2; myb-related protein B [KO:K21769]
110559479  Lin9; protein lin-9 homolog isoform X1 [KO:K21773]
110550946  Lin37; protein lin-37 homolog isoform X1 [KO:K21774]
110546970  Lin52; protein lin-52 homolog isoform X4 [KO:K21775]
110553872  Lin54; protein lin-54 homolog isoform X1 [KO:K21776]
110548589  Rbbp4; histone-binding protein RBBP4 [KO:K10752]
110548625  Foxm1; forkhead box protein M1 isoform X1 [KO:K09406]
110560064  Myc; myc proto-oncogene protein [KO:K04377]
110554386  cyclin-dependent kinase 4 inhibitor B-like [KO:K06621]
110562241  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
110555127  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110550325  Rassf5; ras association domain-containing protein 5 isoform X4 [KO:K08015]
110547815  Fbxw11; F-box/WD repeat-containing protein 11 isoform X5 [KO:K03362]
110556200  Btrc; F-box/WD repeat-containing protein 1A isoform X4 [KO:K03362]
110556734  Hipk4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
110545786  Hipk2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
110546995  Hipk1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
110556835  Hipk3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
110545313  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
110554524  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
110560352  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110557309  Ets1; protein C-ets-1 isoform X2 [KO:K02678]
110561677  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
110563015  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110555604  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110558423  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
110559073  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110555373  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
110566170  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
110560855  Ccnb2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
110542979  Ccnb3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
110547537  Mre11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
110548767  Rad50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
110545061  Nbn; nibrin [KO:K10867]
110549468  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
110553166  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
110560351  Rad9a; cell cycle checkpoint control protein RAD9A isoform X2 [KO:K10994] [EC:3.1.11.2]
110545355  Rad9b; cell cycle checkpoint control protein RAD9B [KO:K10995]
110539951  Rad1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
110556960  Hus1; checkpoint protein HUS1 isoform X1 [KO:K10903]
110539931  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
110549439  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
110565748  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
110557385  Sqstm1; sequestosome-1 [KO:K14381]
110561866  Gata4; transcription factor GATA-4 isoform X1 [KO:K09183]
110561018  Traf3ip2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110551396  Il1a; interleukin-1 alpha [KO:K04383]
110539463  Il6; interleukin-6 [KO:K05405]
110555170  Igfbp3; insulin-like growth factor-binding protein 3 [KO:K10138]
110566254  Serpine1; plasminogen activator inhibitor 1 [KO:K03982]
110550200  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
110550321  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
110546604  Zfp36l1; mRNA decay activator protein ZFP36L1 [KO:K18753]
110558117  Zfp36l2; mRNA decay activator protein ZFP36L2 [KO:K18753]
110547567  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110547289  Trpv4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
110551943  Trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
110549350  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
110546658  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
110561484  Calm1; calmodulin-1 [KO:K02183]
110562918  Calm2; calmodulin-2 [KO:K02183]
110552646  Calm3; calmodulin-3 [KO:K02183]
110550527  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110560701  Calml3; calmodulin-like protein 3 [KO:K02183]
110560702  calmodulin-4-like [KO:K02183]
110555973  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
110551992  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
110551668  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
110558957  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
110561325  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
110550273  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
110547352  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
110545902  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
110543951  Nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
110552142  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
110558908  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110543748  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110556812  Slc25a4; ADP/ATP translocase 1 [KO:K05863]
110566446  Slc25a5; ADP/ATP translocase 2 [KO:K05863]
110566972  Slc25a31; ADP/ATP translocase 4 [KO:K05863]
110558600  Ppid; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
110549632  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
110548867  Vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
110556618  Vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
110557989  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
mun04020  Calcium signaling pathway
mun04068  FoxO signaling pathway
mun04110  Cell cycle
mun04115  p53 signaling pathway
mun04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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