KEGG   PATHWAY: mmu04218
Entry
mmu04218                    Pathway                                
Name
Cellular senescence - Mus musculus (house 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
mmu04218  Cellular senescence
mmu04218

Other DBs
GO: 0090398
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
100529082  H2-T27; histocompatibility 2, T region locus 27 [KO:K06751]
103213  Traf3ip2; TRAF3 interacting protein 2 [KO:K21124]
103583  Fbxw11; F-box and WD-40 domain protein 11 [KO:K03362]
104394  E2f4; E2F transcription factor 4 [KO:K04682]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
110557  H2-Q6; histocompatibility 2, Q region locus 6 [KO:K06751]
110558  H2-Q9; histocompatibility 2, Q region locus 9 [KO:K06751]
110696  H2-M10.3; histocompatibility 2, M region locus 10.3 [KO:K06751]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
11739  Slc25a4; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4 [KO:K05863]
11740  Slc25a5; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5 [KO:K05863]
11920  Atm; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
12192  Zfp36l1; zinc finger protein 36, C3H type-like 1 [KO:K18753]
12193  Zfp36l2; zinc finger protein 36, C3H type-like 2 [KO:K18753]
12234  Btrc; beta-transducin repeat containing protein [KO:K03362]
12289  Cacna1d; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
12313  Calm1; calmodulin 1 [KO:K02183]
12314  Calm2; calmodulin 2 [KO:K02183]
12315  Calm3; calmodulin 3 [KO:K02183]
12333  Capn1; calpain 1 [KO:K01367] [EC:3.4.22.52]
12334  Capn2; calpain 2 [KO:K03853] [EC:3.4.22.53]
12427  Ccna1; cyclin A1 [KO:K06627]
12428  Ccna2; cyclin A2 [KO:K06627]
12442  Ccnb2; cyclin B2 [KO:K21770]
12443  Ccnd1; cyclin D1 [KO:K04503]
12444  Ccnd2; cyclin D2 [KO:K10151]
12445  Ccnd3; cyclin D3 [KO:K10152]
12447  Ccne1; cyclin E1 [KO:K06626]
12448  Ccne2; cyclin E2 [KO:K06626]
12530  Cdc25a; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
12534  Cdk1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
12566  Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
12567  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
12575  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
12578  Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621]
12579  Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685]
12649  Chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
13197  Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
13559  E2f5; E2F transcription factor 5 [KO:K04682]
13685  Eif4ebp1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
14235  Foxm1; forkhead box M1 [KO:K09406]
14463  Gata4; GATA binding protein 4 [KO:K09183]
14963  H2-Bl; histocompatibility 2, blastocyst [KO:K06751]
14964  H2-D1; histocompatibility 2, D region locus 1 [KO:K06751]
14972  H2-K1; histocompatibility 2, K1, K region [KO:K06751]
14980  H2-L; histocompatibility 2, D region locus L [KO:K06751]
14985  H2-M10.1; histocompatibility 2, M region locus 10.1 [KO:K06751]
14990  H2-M2; histocompatibility 2, M region locus 2 [KO:K06751]
14991  H2-M3; histocompatibility 2, M region locus 3 [KO:K06751]
14997  H2-M9; histocompatibility 2, M region locus 9 [KO:K06751]
15006  H2-Q1; histocompatibility 2, Q region locus 1 [KO:K06751]
15007  H2-Q10; histocompatibility 2, Q region locus 10 [KO:K06751]
15013  H2-Q2; histocompatibility 2, Q region locus 2 [KO:K06751]
15015  H2-Q4; histocompatibility 2, Q region locus 4 [KO:K06751]
15018  H2-Q7; histocompatibility 2, Q region locus 7 [KO:K06751]
15024  H2-T10; histocompatibility 2, T region locus 10 [KO:K06751]
15039  H2-T22; histocompatibility 2, T region locus 22 [KO:K06751]
15040  H2-T23; histocompatibility 2, T region locus 23 [KO:K06751]
15042  H2-T24; histocompatibility 2, T region locus 24 [KO:K06751]
15043  H2-T3; histocompatibility 2, T region locus 3 [KO:K06751]
15257  Hipk1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
15258  Hipk2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
15259  Hipk3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
15574  Hus1; HUS1 checkpoint clamp component [KO:K10903]
16009  Igfbp3; insulin-like growth factor binding protein 3 [KO:K10138]
16175  Il1a; interleukin 1 alpha [KO:K04383]
16193  Il6; interleukin 6 [KO:K05405]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
17126  Smad2; SMAD family member 2 [KO:K04500]
17127  Smad3; SMAD family member 3 [KO:K23605]
17164  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
17246  Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
17532  Mras; muscle and microspikes RAS [KO:K07831]
17535  Mre11a; MRE11A homolog A, double strand break repair nuclease [KO:K10865]
17865  Mybl2; myeloblastosis oncogene-like 2 [KO:K21769]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
17873  Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402]
18018  Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
18019  Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18021  Nfatc3; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 3 [KO:K17333]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
18412  Sqstm1; sequestosome 1 [KO:K14381]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18787  Serpine1; serine (or cysteine) peptidase inhibitor, clade E, member 1 [KO:K03982]
19045  Ppp1ca; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
19046  Ppp1cb; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
19047  Ppp1cc; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
19055  Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19057  Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19058  Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
19211  Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
19355  Rad1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
19360  Rad50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
19367  Rad9a; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
19646  Rbbp4; retinoblastoma binding protein 4, chromatin remodeling factor [KO:K10752]
19650  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
19651  Rbl2; RB transcriptional corepressor like 2 [KO:K16332]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
19744  Rheb; Ras homolog enriched in brain [KO:K07208]
20130  Rras; related RAS viral (r-ras) oncogene [KO:K07829]
209091  Ccnb3; cyclin B3 [KO:K21771]
215999  Mcu; mitochondrial calcium uniporter [KO:K20858]
217708  Lin52; lin-52 DREAM MuvB core complex component [KO:K21775]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [KO:K13377]
21812  Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
22059  Trp53; transformation related protein 53 [KO:K04451]
22084  Tsc2; TSC complex subunit 2 [KO:K07207]
22333  Vdac1; voltage-dependent anion channel 1 [KO:K05862]
22334  Vdac2; voltage-dependent anion channel 2 [KO:K15040]
22335  Vdac3; voltage-dependent anion channel 3 [KO:K15041]
224753  H2-M10.4; histocompatibility 2, M region locus 10.4 [KO:K06751]
224754  H2-M11; histocompatibility 2, M region locus 11 [KO:K06751]
224756  H2-M1; histocompatibility 2, M region locus 1 [KO:K06751]
224761  H2-M10.5; histocompatibility 2, M region locus 10.5 [KO:K06751]
231506  Lin54; lin-54 DREAM MuvB core complex component [KO:K21776]
231724  Rad9b; RAD9 checkpoint clamp component B [KO:K10995]
233020  Hipk4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
23871  Ets1; E26 avian leukemia oncogene 1, 5' domain [KO:K02678]
23882  Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402]
240095  H2-M5; histocompatibility 2, M region locus 5 [KO:K06751]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
245000  Atr; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26397  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
268697  Ccnb1; cyclin B1 [KO:K05868]
27354  Nbn; nibrin [KO:K10867]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
333473  Zfp36l3; zinc finger protein 36, C3H type-like 3 [KO:K18753]
333715  H2-M10.2; histocompatibility 2, M region locus 10.2 [KO:K06751]
399549  H2-M10.6; histocompatibility 2, M region locus 10.6 [KO:K06751]
434175  Ccnb1-ps; cyclin B1, pseudogene [KO:K05868]
434233  Ppp1ccb; protein phosphatase 1 catalytic subunit gamma B [KO:K06269] [EC:3.1.3.16]
494124  Calm5; calmodulin 5 [KO:K02183]
50883  Chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
54354  Rassf5; Ras association (RalGDS/AF-6) domain family member 5 [KO:K08015]
547349  H2-K1; MHC class I family member [KO:K06751]
56458  Foxo1; forkhead box O1 [KO:K07201]
56484  Foxo3; forkhead box O3 [KO:K09408]
56717  Mtor; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
58800  Trpm7; transient receptor potential cation channel, subfamily M, member 7 [KO:K04982] [EC:2.7.11.1]
630294  H2-T25; histocompatibility-2, T region locus 25 [KO:K06751]
63873  Trpv4; transient receptor potential cation channel, subfamily V, member 4 [KO:K04973]
64930  Tsc1; TSC complex subunit 1 [KO:K07206]
667977  H2-T26; histocompatibility 2, T region locus 26 [KO:K06751]
66922  Rras2; related RAS viral (r-ras) oncogene 2 [KO:K07830]
67738  Ppid; peptidylprolyl isomerase D (cyclophilin D) [KO:K05864] [EC:5.2.1.8]
69717  Gm10499; predicted gene 10499 [KO:K06751]
70405  Calml3; calmodulin-like 3 [KO:K02183]
72568  Lin9; lin-9 DREAM MuvB core complex component [KO:K21773]
73181  Nfatc4; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4 [KO:K17334]
73333  Slc25a31; solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31 [KO:K05863]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
75600  Calml4; calmodulin-like 4 [KO:K02183]
75660  Lin37; lin-37 DREAM MuvB core complex component [KO:K21774]
80796  Calm4; calmodulin 4 [KO:K02183]
93759  Sirt1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
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
mmu04020  Calcium signaling pathway
mmu04068  FoxO signaling pathway
mmu04110  Cell cycle
mmu04115  p53 signaling pathway
mmu04150  mTOR signaling pathway
KO pathway
ko04218   

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