KEGG   PATHWAY: ptg04218
Entry
ptg04218                    Pathway                                
Name
Cellular senescence - Panthera tigris altaica (Amur tiger)
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
ptg04218  Cellular senescence
ptg04218

Other DBs
GO: 0090398
Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102951285  TGFB1; transforming growth factor beta 1 [KO:K13375]
102951894  TGFB2; transforming growth factor beta 2 [KO:K13376]
102949760  TGFB3; transforming growth factor beta 3 [KO:K13377]
102950020  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102958413  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102971687  SMAD2; SMAD family member 2 [KO:K04500]
102971888  SMAD3; SMAD family member 3 [KO:K23605]
102970281  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102967948  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102959906  CCND1; cyclin D1 [KO:K04503]
102970259  CCND2; cyclin D2 [KO:K10151]
102970915  CCND3; cyclin D3 [KO:K10152]
102952365  RB1; RB transcriptional corepressor 1 [KO:K06618]
102968045  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102970305  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102963506  E2F1; E2F transcription factor 1 [KO:K17454]
102952251  E2F2; E2F transcription factor 2 [KO:K09389]
102948948  E2F3; E2F transcription factor 3 [KO:K06620]
102956308  E2F4; E2F transcription factor 4 [KO:K04682]
102954744  E2F5; E2F transcription factor 5 [KO:K04682]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102969147  FOXO1; forkhead box O1 [KO:K07201]
102961930  FOXO3; forkhead box O3 [KO:K09408]
102964051  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102959572  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102955833  CCNE2; cyclin E2 [KO:K06626]
102966425  CCNE1; cyclin E1 [KO:K06626]
102959211  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
102970351  class I histocompatibility antigen, Gogo-B*0101 alpha chain-like [KO:K06751]
102970631  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
102958279  class I histocompatibility antigen, Gogo-B*0101 alpha chain-like [KO:K06751]
102965588  class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751]
102965871  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
102961195  HLA class I histocompatibility antigen, A-11 alpha chain-like [KO:K06751]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102968314  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
102967033  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102970438  MRAS; muscle RAS oncogene homolog [KO:K07831]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102953770  TSC1; tuberous sclerosis 1 [KO:K07206]
102956176  TSC2; tuberous sclerosis 2 [KO:K07207]
102970146  RHEB; Ras homolog enriched in brain [KO:K07208]
102967196  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102972446  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102963908  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
102970677  CCNA1; cyclin A1 [KO:K06627]
102970341  CCNA2; cyclin A2 [KO:K06627]
102952697  MYBL2; MYB proto-oncogene like 2 [KO:K21769]
102971369  LIN9; protein lin-9 homolog [KO:K21773]
102951060  protein lin-9 homolog [KO:K21773]
102960894  LIN37; lin-37 DREAM MuvB core complex component [KO:K21774]
102961262  LIN52; lin-52 DREAM MuvB core complex component [KO:K21775]
102964384  LIN54; lin-54 DREAM MuvB core complex component [KO:K21776]
102970360  RBBP4; RB binding protein 4, chromatin remodeling factor [KO:K10752]
102966195  FOXM1; forkhead box M1 [KO:K09406]
102954147  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102965880  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102962571  TP53; tumor protein p53 [KO:K04451]
102963911  RASSF5; Ras association domain family member 5 [KO:K08015]
102962015  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
102953972  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
102952809  HIPK2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
102953517  HIPK3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
102955575  HIPK1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
102962072  HIPK4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102948702  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
107180886  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102970154  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102967030  ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678]
102949954  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102966485  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102968191  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102960306  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102960590  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102968482  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102964763  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102951885  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102971079  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102952704  CCNB1; cyclin B1 [KO:K05868]
102951958  CCNB2; cyclin B2 [KO:K21770]
102969495  CCNB3; cyclin B3 [KO:K21771]
102965377  MRE11; MRE11 homolog, double strand break repair nuclease [KO:K10865]
102964063  RAD50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
102950092  NBN; nibrin [KO:K10867]
102958898  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102960814  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102952886  RAD9A; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
102953389  RAD9B; RAD9 checkpoint clamp component B [KO:K10995]
102955874  RAD1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
102953450  HUS1; HUS1 checkpoint clamp component [KO:K10903]
102972858  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102948766  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102957057  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102964239  SQSTM1; sequestosome 1 [KO:K14381]
102968051  GATA4; GATA binding protein 4 [KO:K09183]
102957091  TRAF3IP2; TRAF3 interacting protein 2 [KO:K21124]
102964232  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102951132  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102951574  IL1A; interleukin 1 alpha [KO:K04383]
102968780  IL6; interleukin 6 [KO:K05405]
102953898  interleukin-8-like [KO:K10030]
102953024  IL8; interleukin-8 [KO:K10030]
102961146  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
102972312  SERPINE1; serpin family E member 1 [KO:K03982]
102961839  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
102961644  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102965752  ZFP36L1; ZFP36 ring finger protein like 1 [KO:K18753]
102958456  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102961441  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102955453  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102953457  CALM3; calmodulin 3 [KO:K02183]
102963939  calmodulin-like [KO:K02183]
102964234  CALML3; calmodulin-like protein 3 [KO:K02183]
102954552  CALM2; calmodulin 2 [KO:K02183]
102960923  calmodulin-like [KO:K02183]
102950842  CALML6; calmodulin like 6 [KO:K02183]
102951822  CALM1; calmodulin 1 [KO:K02183]
102971520  calmodulin-alpha-like [KO:K02183]
102950182  CALML4; calmodulin like 4 [KO:K02183]
102952632  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102949359  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102963447  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102965200  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102967427  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102969678  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102972106  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102956831  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102963245  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102971840  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102967639  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102960718  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
102966182  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
102972215  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
102971432  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
102962163  ADP/ATP translocase 2-like [KO:K05863]
102950091  PPID; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
102959401  VDAC1; voltage dependent anion channel 1 [KO:K05862]
102951163  VDAC2; voltage dependent anion channel 2 [KO:K15040]
102962706  VDAC3; voltage dependent anion channel 3 [KO:K15041]
102969716  MCU; mitochondrial calcium uniporter [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
ptg04020  Calcium signaling pathway
ptg04068  FoxO signaling pathway
ptg04110  Cell cycle
ptg04115  p53 signaling pathway
ptg04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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