KEGG   PATHWAY: afz04218
Entry
afz04218                    Pathway                                
Name
Cellular senescence - Antechinus flavipes (yellow-footed antechinus)
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
afz04218  Cellular senescence
afz04218

Other DBs
GO: 0090398
Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127556228  transforming growth factor beta-1 proprotein [KO:K13375]
127562518  transforming growth factor beta-2 proprotein [KO:K13376]
127549479  transforming growth factor beta-3 proprotein [KO:K13377]
127541471  TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
127538005  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
127543521  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
127551234  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
127545332  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
127538222  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
127537888  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
127539835  G1/S-specific cyclin-D1 [KO:K04503]
127539247  G1/S-specific cyclin-D2 [KO:K10151]
127561736  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
127555178  retinoblastoma-associated protein isoform X1 [KO:K06618]
127550410  retinoblastoma-like protein 1 [KO:K04681]
127550708  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
127550324  transcription factor E2F1 [KO:K17454]
127555707  transcription factor E2F2 [KO:K09389]
127544127  transcription factor E2F3 [KO:K06620]
127543711  transcription factor E2F5 [KO:K04682]
127547919  transcription factor E2F4 isoform X1 [KO:K04682]
127555896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127552891  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
127554245  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127563398  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
127558297  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
127545225  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127555224  forkhead box protein O1 [KO:K07201]
127562063  forkhead box protein O3 [KO:K09408]
127561515  cyclin-dependent kinase inhibitor 1 [KO:K06625]
127564952  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
127550660  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
127544298  G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
127561112  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
127561627  DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]
127561733  class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751]
127561629  patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751]
127564364  ras-like protein [KO:K07827]
127564665  ras-like protein [KO:K07827]
127564806  GTPase KRas isoform X1 [KO:K07827]
127564858  GTPase KRas-like [KO:K07827]
127564890  ras-like protein [KO:K07827]
127564892  GTPase NRas-like [KO:K07827]
127541495  ras-like protein [KO:K07827]
127537819  GTPase NRas-like [KO:K07827]
127537860  GTPase NRas-like [KO:K07827]
127538037  ras-like protein [KO:K07827]
127538119  ras-like protein [KO:K07827]
127538128  LOW QUALITY PROTEIN: ras-like protein [KO:K07827]
127538787  ras-like protein [KO:K07827]
127538953  ras-like protein [KO:K07827]
127539191  ras-like protein [KO:K07827]
127539349  GTPase NRas-like [KO:K07827]
127539435  ras-like protein [KO:K07827]
127539441  ras protein let-60-like [KO:K07827]
127541494  ras-like protein [KO:K07828]
127559280  GTPase NRas [KO:K07828]
127538788  GTPase NRas-like [KO:K07828]
127538790  GTPase NRas-like [KO:K07828]
127538791  GTPase NRas-like [KO:K07828]
127538792  GTPase NRas-like [KO:K07828]
127538794  GTPase NRas-like [KO:K07828]
127556578  ras-related protein R-Ras [KO:K07829]
127539691  ras-related protein R-Ras2 [KO:K07830]
127554241  ras-related protein M-Ras [KO:K07831]
127540068  GTPase HRas [KO:K02833]
127549861  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127556193  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127559596  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127550929  hamartin isoform X1 [KO:K07206]
127543419  tuberin isoform X1 [KO:K07207]
127539348  GTP-binding protein Rheb [KO:K07208]
127555875  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
127552159  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]
127552112  NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
127541195  cyclin-A2 [KO:K06627]
127555246  cyclin-A1 isoform X1 [KO:K06627]
127550388  myb-related protein B isoform X1 [KO:K21769]
127559545  protein lin-9 homolog isoform X1 [KO:K21773]
127556081  protein lin-37 homolog isoform X1 [KO:K21774]
127549520  protein lin-52 homolog isoform X1 [KO:K21775]
127539766  protein lin-54 homolog [KO:K21776]
127555516  histone-binding protein RBBP4 isoform X1 [KO:K10752]
127564129  forkhead box protein M1 isoform X1 [KO:K09406]
127544452  myc proto-oncogene protein [KO:K04377]
127564477  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
127538796  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
127560870  cellular tumor antigen p53 isoform X1 [KO:K04451]
127562634  ras association domain-containing protein 5 isoform X1 [KO:K08015]
127550198  F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
127551491  F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
127541213  homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
127556188  homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
127559294  homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
127539351  homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
127541293  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
127545469  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
127548703  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
127552087  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
127551242  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127544950  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
127556083  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
127545795  mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
127554816  protein C-ets-1 [KO:K02678]
127563289  dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
127560548  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
127538834  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
127538838  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
127561225  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
127561226  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
127563174  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
127545137  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
127552133  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
127552134  cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
127558326  G2/mitotic-specific cyclin-B1 [KO:K05868]
127551202  G2/mitotic-specific cyclin-B2 [KO:K21770]
127549849  DNA repair protein RAD50-like isoform X1 [KO:K10866] [EC:3.6.-.-]
127544265  nibrin isoform X1 [KO:K10867]
127554958  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
127545635  serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
127541292  cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
127548486  cell cycle checkpoint control protein RAD9B [KO:K10995]
127556462  cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
127553609  checkpoint protein HUS1 isoform X1 [KO:K10903]
127552991  serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
127554847  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
127550315  sequestosome-1 isoform X1 [KO:K14381]
127548521  transcription factor GATA-4 [KO:K09183]
127562102  E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
127541094  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127540746  transcription factor p65 isoform X1 [KO:K04735]
127547604  interleukin-1 alpha isoform X1 [KO:K04383]
127540720  interleukin-8 [KO:K10030]
127553634  insulin-like growth factor-binding protein 3 [KO:K10138]
127560959  plasminogen activator inhibitor 1 [KO:K03982]
127548228  eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
127562627  MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
127549667  mRNA decay activator protein ZFP36L1 [KO:K18753]
127548028  mRNA decay activator protein ZFP36L2 isoform X1 [KO:K18753]
127550201  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
127545603  transient receptor potential cation channel subfamily V member 4 [KO:K04973]
127551146  transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
127541787  calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
127559523  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
127564795  calmodulin-A-like [KO:K02183]
127549410  calmodulin-1 [KO:K02183]
127555994  calmodulin-like protein 6 [KO:K02183]
127556283  calmodulin-3 [KO:K02183]
127551228  calmodulin-like protein 4 isoform X1 [KO:K02183]
127548058  calmodulin-2 [KO:K02183]
127551919  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127548327  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127540919  protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
127548157  calcineurin subunit B type 1 isoform X1 [KO:K06268]
127544078  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
127548924  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
127547866  nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
127551102  nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
127551451  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127539174  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127561144  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127549804  ADP/ATP translocase 3 [KO:K05863]
127538715  ADP/ATP translocase 3-like [KO:K05863]
127539964  ADP/ATP translocase 4 [KO:K05863]
127553688  ADP/ATP translocase 3 [KO:K05863]
127540685  ADP/ATP translocase 1 [KO:K05863]
127549828  voltage-dependent anion-selective channel protein 1 [KO:K05862]
127541140  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
127551885  voltage-dependent anion-selective channel protein 2 [KO:K15040]
127548278  voltage-dependent anion-selective channel protein 3 [KO:K15041]
127551934  calcium uniporter protein, mitochondrial [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
afz04020  Calcium signaling pathway
afz04068  FoxO signaling pathway
afz04110  Cell cycle
afz04115  p53 signaling pathway
afz04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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