KEGG   PATHWAY: ccay04218
Entry
ccay04218                   Pathway                                
Name
Cellular senescence - Caretta caretta (Loggerhead turtle)
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
ccay04218  Cellular senescence
ccay04218

Other DBs
GO: 0090398
Organism
Caretta caretta (Loggerhead turtle) [GN:ccay]
Gene
125628071  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
125633641  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
125639078  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
125631915  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
125631639  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
125645204  LOW QUALITY PROTEIN: TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
125636648  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
125643757  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
125636630  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
125636631  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
125627703  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
125631434  cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
125638229  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
125623801  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
125624926  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
125636578  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
125622408  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
125645297  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
125622290  E2F1; transcription factor E2F1 [KO:K17454]
125624789  E2F2; transcription factor E2F2 [KO:K09389]
125632188  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
125632614  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
125645299  E2F4; transcription factor E2F4 [KO:K04682]
125642142  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125628531  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
125642447  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125624203  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125626958  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
125640830  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
125636597  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125636017  FOXO1; forkhead box protein O1 [KO:K07201]
125634307  FOXO3; forkhead box protein O3 isoform X1 [KO:K09408]
125624087  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
125624994  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
125627631  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
125620709  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
125632681  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
125621124  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
125629591  class I histocompatibility antigen, F10 alpha chain-like isoform X1 [KO:K06751]
125629604  class I histocompatibility antigen, F10 alpha chain-like isoform X1 [KO:K06751]
125621134  LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q9 alpha chain-like [KO:K06751]
125628281  GTPase HRas-like [KO:K07827]
125624971  KRAS; GTPase KRas isoform X1 [KO:K07827]
125625144  NRAS; GTPase NRas [KO:K07828]
125628495  RRAS; ras-related protein R-Ras [KO:K07830]
125639064  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
125644951  MRAS; ras-related protein M-Ras [KO:K07831]
125637699  HRAS; GTPase HRas [KO:K02833]
125633846  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125628110  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125638191  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125623530  TSC1; hamartin isoform X1 [KO:K07206]
125643570  TSC2; tuberin isoform X1 [KO:K07207]
125631217  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
125624346  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
125639423  PTEN; 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]
125635472  CCNA2; cyclin-A2 [KO:K06627]
125635761  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
125622347  MYBL2; myb-related protein B isoform X1 [KO:K21769]
125633698  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
125626122  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
125639243  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
125635756  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
125624682  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
125623634  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
125632839  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
125630218  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
125628652  TP53; cellular tumor antigen p53 [KO:K04451]
125625190  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
125640567  BTRC; LOW QUALITY PROTEIN: F-box/WD repeat-containing protein 1A [KO:K03362]
125641081  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
125627226  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
125628109  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
125638134  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
125624942  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
125633732  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
125622712  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
125638317  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
125640538  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125644013  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125627064  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125623233  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
125638210  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125625401  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
125643689  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
125621197  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
125630653  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
125630656  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
125625009  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125625183  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125627123  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
125641559  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
125637066  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
125640343  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
125637181  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
125644101  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
125633630  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
125641419  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
125632638  NBN; nibrin isoform X1 [KO:K10867]
125634149  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
125622921  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
125638316  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
125623085  RAD9B; LOW QUALITY PROTEIN: cell cycle checkpoint control protein RAD9B [KO:K10995]
125636741  RAD1; cell cycle checkpoint protein RAD1 isoform X1 [KO:K02830] [EC:3.1.11.2]
125631864  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
125642637  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
125625503  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
125632997  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
125641938  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
125634705  GATA4; transcription factor GATA-4 [KO:K09183]
125634269  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 [KO:K21124]
125635313  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125639301  RELA; transcription factor p65 isoform X1 [KO:K04735]
125631011  IL6; interleukin-6 [KO:K05405]
125635330  interleukin-8-like [KO:K10030]
125635331  interleukin-8-like [KO:K10030]
125635332  interleukin-8-like [KO:K10030]
125636109  interleukin-8-like [KO:K10030]
125631859  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
125628741  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
125626331  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 isoform X1 [KO:K07205]
125625189  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:2.7.11.1]
125633568  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
125628244  mRNA decay activator protein ZFP36L1-like [KO:K18753]
125637614  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
125639955  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
125623035  TRPV4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
125643965  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
125639557  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
125633779  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
125633672  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
125633502  CALM2; calmodulin-2 [KO:K02183]
125640639  calmodulin-A isoform X1 [KO:K02183]
125628181  CALM3; calmodulin-3 [KO:K02183]
125643358  CALML4; calmodulin-like protein 4 [KO:K02183]
125624266  CALML6; calmodulin-like protein 6 [KO:K02183]
125637734  CALM1; calmodulin-1 [KO:K02183]
125626346  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
125640009  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
125635376  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
125633448  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
125632217  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
125622354  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
125645342  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
125622431  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
125639566  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125624778  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125625000  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
125640751  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
125635530  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
125635808  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
125642881  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
125635627  PPID; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
125641618  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
125639607  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
125626302  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
125639890  MCU; 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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
ccay04020  Calcium signaling pathway
ccay04068  FoxO signaling pathway
ccay04110  Cell cycle
ccay04115  p53 signaling pathway
ccay04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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