KEGG   PATHWAY: bom04218
Entry
bom04218                    Pathway                                
Name
Cellular senescence - Bos mutus (wild yak)
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
bom04218  Cellular senescence
bom04218

Other DBs
GO: 0090398
Organism
Bos mutus (wild yak) [GN:bom]
Gene
102283357  TGFB1; transforming growth factor beta 1 [KO:K13375]
102283491  TGFB2; transforming growth factor beta 2 [KO:K13376]
102265567  TGFB3; transforming growth factor beta 3 [KO:K13377]
102283685  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102267018  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102286495  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102282627  SMAD3; SMAD family member 3 [KO:K23605]
102278545  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102264992  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102270546  CCND1; cyclin D1 [KO:K04503]
102272576  CCND2; cyclin D2 [KO:K10151]
102268077  CCND3; cyclin D3 [KO:K10152]
102267169  RB1; RB transcriptional corepressor 1 [KO:K06618]
102286105  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102271403  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102274863  E2F1; E2F transcription factor 1 [KO:K17454]
102268181  E2F2; E2F transcription factor 2 [KO:K09389]
102270876  E2F3; E2F transcription factor 3 [KO:K06620]
102281676  E2F5; E2F transcription factor 5 [KO:K04682]
102271624  E2F4; E2F transcription factor 4 [KO:K04682]
102274553  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102274461  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102277548  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102266922  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102280296  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102286868  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102284612  FOXO1; forkhead box O1 [KO:K07201]
102287014  FOXO3; forkhead box O3 [KO:K09408]
102268672  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102277344  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102284697  CCNE2; cyclin E2 [KO:K06626]
102271261  CCNE1; cyclin E1 [KO:K06626]
102288356  H-2 class I histocompatibility antigen, Q10 alpha chain [KO:K06751]
102275624  BOLA class I histocompatibility antigen, alpha chain BL3-6-like [KO:K06751]
102268170  BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751]
102278231  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
102286220  BOLA class I histocompatibility antigen, alpha chain BL3-6 [KO:K06751]
102286791  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
102281193  BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751]
102272326  BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751]
102270654  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
102286500  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102269203  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102279307  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
102283530  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102276240  MRAS; muscle RAS oncogene homolog [KO:K07831]
102278591  GTPase HRas [KO:K02833]
102277011  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102275199  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102265427  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102283212  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102280709  TSC1; tuberous sclerosis 1 [KO:K07206]
102267343  TSC2; tuberous sclerosis 2 [KO:K07207]
102277658  RHEB; Ras homolog enriched in brain [KO:K07208]
102267219  GTP-binding protein Rheb [KO:K07208]
102281727  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102268478  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102276604  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
102274455  CCNA2; cyclin A2 [KO:K06627]
102276514  CCNA1; cyclin A1 [KO:K06627]
102280182  MYBL2; MYB proto-oncogene like 2 [KO:K21769]
102271467  LIN9; lin-9 DREAM MuvB core complex component [KO:K21773]
102277935  LIN37; lin-37 DREAM MuvB core complex component [KO:K21774]
102276828  LIN52; lin-52 DREAM MuvB core complex component [KO:K21775]
102277046  LIN54; lin-54 DREAM MuvB core complex component [KO:K21776]
102268474  RBBP4; RB binding protein 4, chromatin remodeling factor [KO:K10752]
102266685  forkhead box protein M1-like [KO:K09406]
102287371  FOXM1; forkhead box M1 [KO:K09406]
102274304  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102284461  CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621]
102287490  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102272370  TP53; tumor protein p53 [KO:K04451]
102271221  RASSF5; Ras association domain family member 5 [KO:K08015]
102280912  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
102273208  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
102276621  HIPK4; homeodomain interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102267073  HIPK1; homeodomain interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
102278306  HIPK3; homeodomain interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
102269280  HIPK2; homeodomain interacting protein kinase 2 [KO:K08826] [EC:2.7.11.1]
102270793  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102275429  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102266876  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102288216  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102280670  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102271710  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102267789  ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678]
102267773  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102272962  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102271030  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102271320  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
106701244  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102285848  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102276116  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102266978  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102288000  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102287071  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102264536  CCNB1; cyclin B1 [KO:K05868]
102284855  CCNB2; cyclin B2 [KO:K21770]
102276872  CCNB3; cyclin B3 [KO:K21771]
102268755  MRE11; MRE11 homolog, double strand break repair nuclease [KO:K10865]
102272621  RAD50; RAD50 double strand break repair protein [KO:K10866] [EC:3.6.-.-]
102268487  NBN; nibrin [KO:K10867]
102278968  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
102270218  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
102283552  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102287638  RAD9A; RAD9 checkpoint clamp component A [KO:K10994] [EC:3.1.11.2]
102278073  RAD9B; RAD9 checkpoint clamp component B [KO:K10995]
102271337  RAD1; RAD1 checkpoint DNA exonuclease [KO:K02830] [EC:3.1.11.2]
102287786  HUS1; HUS1 checkpoint clamp component [KO:K10903]
102268491  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102266500  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102285046  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102279447  SQSTM1; sequestosome 1 [KO:K14381]
102284081  GATA4; GATA binding protein 4 [KO:K09183]
102284665  TRAF3IP2; TRAF3 interacting protein 2 [KO:K21124]
102286969  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102268417  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102282330  IL1A; interleukin 1 alpha [KO:K04383]
102287919  IL6; interleukin 6 [KO:K05405]
102268124  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102288361  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
102275884  SERPINE1; serpin family E member 1 [KO:K03982]
102278368  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
102274647  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102287358  ZFP36L1; ZFP36 ring finger protein like 1 [KO:K18753]
102288114  ZFP36L2; ZFP36 ring finger protein like 2 [KO:K18753]
102271623  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102272539  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102278251  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102283099  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
102276298  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
102280361  calmodulin-alpha [KO:K02183]
102285968  CALML6; calmodulin like 6 [KO:K02183]
102281667  CALM1; calmodulin 1 [KO:K02183]
102287375  calmodulin [KO:K02183]
102268061  CALM2; calmodulin 2 [KO:K02183]
102265605  calmodulin-alpha [KO:K02183]
102266295  calmodulin [KO:K02183]
102282476  CALM3; calmodulin 3 [KO:K02183]
102269657  CALML3; calmodulin-like protein 3 [KO:K02183]
102271961  calmodulin-2/4-like [KO:K02183]
102284406  CALML4; calmodulin like 4 [KO:K02183]
102275863  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102286752  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102266749  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102272271  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102277736  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102286049  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102285474  nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446]
102277605  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102281905  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102285411  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102269088  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102269013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102271039  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102275932  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
102286445  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
102280125  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
102287077  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
102271597  PPID; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
102266916  VDAC1; voltage dependent anion channel 1 [KO:K05862]
102281314  VDAC2; voltage dependent anion channel 2 [KO:K15040]
102280707  VDAC3; voltage dependent anion channel 3 [KO:K15041]
102264532  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
bom04020  Calcium signaling pathway
bom04068  FoxO signaling pathway
bom04110  Cell cycle
bom04115  p53 signaling pathway
bom04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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