KEGG   PATHWAY: ocu04218
Entry
ocu04218                    Pathway                                
Name
Cellular senescence - Oryctolagus cuniculus (rabbit)
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
ocu04218  Cellular senescence
ocu04218

Other DBs
GO: 0090398
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100352301  LOW QUALITY PROTEIN: transforming growth factor beta-1 proprotein [KO:K13375]
103345448  transforming growth factor beta-1 proprotein isoform X9 [KO:K13375]
100008645  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100009371  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100358982  transforming growth factor beta-3 proprotein [KO:K13377]
100345812  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100344335  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
100359137  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100346303  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100351874  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100009039  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100009040  cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
100009036  G1/S-specific cyclin-D2 [KO:K10151]
100009038  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100357431  retinoblastoma-associated protein isoform X1 [KO:K06618]
100342365  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100339977  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100356957  transcription factor E2F1 [KO:K17454]
127489175  LOW QUALITY PROTEIN: transcription factor E2F1-like [KO:K17454]
100346379  transcription factor E2F2 [KO:K09389]
100353173  transcription factor E2F3 isoform X1 [KO:K06620]
100348976  transcription factor E2F5 [KO:K04682]
100344311  transcription factor E2F4 [KO:K04682]
100348051  transcription factor E2F4 [KO:K04682]
100348663  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100345181  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100337822  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100357841  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100345250  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100358471  LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
100343573  forkhead box protein O3 [KO:K09408]
100348489  cyclin-dependent kinase inhibitor 1 [KO:K06625]
100134865  cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
127487420  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
100134864  G1/S-specific cyclin-E1 [KO:K06626]
100134867  G1/S-specific cyclin-E2 isoform X3 [KO:K06626]
100354611  H-2 class I histocompatibility antigen, Q10 alpha chain isoform X4 [KO:K06751]
100338822  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100349085  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100339821  LOW QUALITY PROTEIN: RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100348995  RLA class I histocompatibility antigen, alpha chain 11/11 isoform X16 [KO:K06751]
100355380  patr class I histocompatibility antigen, A-2 alpha chain isoform X2 [KO:K06751]
100349247  HLA class I histocompatibility antigen, B alpha chain isoform X2 [KO:K06751]
100349757  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100328967  RLA class I histocompatibility antigen, alpha chain 19-1 precursor [KO:K06751]
100356371  RLA-A3; MHC class I antigen-like precursor [KO:K06751]
100347487  GTPase KRas isoform X1 [KO:K07827]
127489236  GTPase KRas-like [KO:K07827]
100344241  GTPase NRas [KO:K07828]
127489362  ras-related protein R-Ras [KO:K07829]
100355920  ras-related protein R-Ras2 [KO:K07830]
100358182  ras-related protein M-Ras isoform X1 [KO:K07831]
127486605  GTPase HRas isoform X1 [KO:K02833]
100342852  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100353706  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127486116  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100338695  hamartin [KO:K07206]
100351640  tuberin isoform X1 [KO:K07207]
100348492  GTP-binding protein Rheb [KO:K07208]
100356164  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100358716  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100349271  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100358389  cyclin-A1 isoform X1 [KO:K06627]
100134866  CCNA2; cyclin-A2 [KO:K06627]
100352785  cyclin-A2-like [KO:K06627]
100346753  myb-related protein B [KO:K21769]
100353949  protein lin-9 homolog [KO:K21773]
100347701  protein lin-37 homolog isoform X1 [KO:K21774]
103351685  protein lin-52 homolog isoform X2 [KO:K21775]
100341285  protein lin-54 homolog isoform X2 [KO:K21776]
100341469  histone-binding protein RBBP4 isoform X1 [KO:K10752]
100353085  LOW QUALITY PROTEIN: histone-binding protein RBBP4-like [KO:K10752]
100358944  forkhead box protein M1 isoform X4 [KO:K09406]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100340625  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
100009292  TP53; cellular tumor antigen p53 [KO:K04451]
100345444  ras association domain-containing protein 5 isoform X1 [KO:K08015]
100340737  F-box/WD repeat-containing protein 11 isoform X4 [KO:K03362]
100350519  F-box/WD repeat-containing protein 1A isoform X4 [KO:K03362]
100359086  homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
100341141  homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
100339292  homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
100346212  homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
100009587  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100009298  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100353054  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100347407  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100009316  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127489461  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
100347345  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100348561  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100009373  ETS1; protein C-ets-1 [KO:K02678]
100339953  dual specificity mitogen-activated protein kinase kinase 3 isoform X3 [KO:K04432] [EC:2.7.12.2]
100355230  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
100350614  mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
103346035  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
100344161  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100341695  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100353284  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100353742  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100352863  cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100338989  G2/mitotic-specific cyclin-B1 [KO:K05868]
100357416  G2/mitotic-specific cyclin-B2 [KO:K21770]
100356406  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
100356946  MRE11; double-strand break repair protein MRE11 [KO:K10865]
100328725  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
100352398  nibrin isoform X1 [KO:K10867]
100349299  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100339430  serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
100356526  cell cycle checkpoint control protein RAD9A isoform X5 [KO:K10994] [EC:3.1.11.2]
100358383  cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
100351835  cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
100357438  checkpoint protein HUS1 isoform X1 [KO:K10903]
100359062  serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
100345729  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
100354280  M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
100342157  sequestosome-1 isoform X1 [KO:K14381]
100008858  transcription factor GATA-4 isoform X2 [KO:K09183]
100338995  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
100349426  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127485184  transcription factor p65 isoform X1 [KO:K04735]
100009250  IL1A; interleukin-1 alpha [KO:K04383]
100008733  IL6; interleukin-6 precursor [KO:K05405]
100009129  CXCL8; interleukin-8 precursor [KO:K10030]
127485419  insulin-like growth factor-binding protein 3 [KO:K10138]
100009588  plasminogen activator inhibitor 1 [KO:K03982]
100338850  eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100009438  MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100349183  mRNA decay activator protein ZFP36L1 [KO:K18753]
100351567  LOW QUALITY PROTEIN: mRNA decay activator protein ZFP36L2 [KO:K18753]
100327259  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100351058  transient receptor potential cation channel subfamily V member 4 [KO:K04973]
100350932  LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
100009089  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
100009092  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103345165  LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]
100347856  calmodulin-like protein 3 [KO:K02183]
100354905  calmodulin-3 [KO:K02183]
100352392  CALM2; calmodulin [KO:K02183]
100350107  calmodulin-1 [KO:K02183]
100345526  calmodulin-like protein 4 isoform X1 [KO:K02183]
100356245  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100009423  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
100009487  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
100344533  calcineurin subunit B type 2 [KO:K06268]
100352378  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
100353824  nuclear factor of activated T-cells, cytoplasmic 2 isoform X3 [KO:K17332]
100008859  nuclear factor of activated T-cells, cytoplasmic 3 isoform X2 [KO:K17333]
100347003  nuclear factor of activated T-cells, cytoplasmic 4 isoform X2 [KO:K17334]
100009505  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100356806  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100008939  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100346477  ADP/ATP translocase 4 isoform X1 [KO:K05863]
100009414  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
100349768  ADP/ATP translocase 1 [KO:K05863]
100356326  ADP/ATP translocase 2 [KO:K05863]
100337764  ADP/ATP translocase 2 [KO:K05863]
100342972  ADP/ATP translocase 2-like [KO:K05863]
100348057  ADP/ATP translocase 2-like [KO:K05863]
100354802  ADP/ATP translocase 2-like [KO:K05863]
100340606  peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
100008751  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
100349506  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
100009473  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
100008752  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
100341372  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
ocu04020  Calcium signaling pathway
ocu04068  FoxO signaling pathway
ocu04110  Cell cycle
ocu04115  p53 signaling pathway
ocu04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

DBGET integrated database retrieval system