KEGG   PATHWAY: ccad04218
Entry
ccad04218                   Pathway                                
Name
Cellular senescence - Cervus canadensis (wapiti)
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
ccad04218  Cellular senescence
ccad04218

Other DBs
GO: 0090398
Organism
Cervus canadensis (wapiti) [GN:ccad]
Gene
122420314  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
122452400  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122443885  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
122453210  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
122424266  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
122425874  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
122443073  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
122452872  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122427215  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
122438094  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122430666  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
122424006  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
122429373  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
122447603  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
122447910  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
122420237  RBL2; retinoblastoma-like protein 2 [KO:K16332]
122448331  E2F1; transcription factor E2F1 [KO:K17454]
122426579  E2F2; transcription factor E2F2 [KO:K09389]
122429389  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
122421728  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
122451088  E2F5; transcription factor E2F5 [KO:K04682]
122451688  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122445271  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122444906  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122440740  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122454626  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122437038  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
122447047  FOXO1; forkhead box protein O1 isoform X1 [KO:K07201]
122422901  FOXO3; forkhead box protein O3 isoform X1 [KO:K09408]
122429747  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122427513  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122421575  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
122450896  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
122429624  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
122429686  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
122429691  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
122440883  uncharacterized protein LOC122440883 [KO:K06751]
122440005  H-2 class I histocompatibility antigen, alpha chain-like [KO:K06751]
122429593  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
122429603  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
122423876  KRAS; GTPase KRas isoform X1 [KO:K07827]
122446047  GTPase KRas [KO:K07827]
122435924  NRAS; GTPase NRas [KO:K07828]
122421012  RRAS; ras-related protein R-Ras [KO:K07829]
122449591  RRAS2; ras-related protein R-Ras2 [KO:K07830]
122438934  ras-related protein R-Ras2-like [KO:K07830]
122445280  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
122430591  HRAS; GTPase HRas isoform X1 [KO:K02833]
122420500  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122452448  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122455107  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122442300  TSC1; hamartin isoform X1 [KO:K07206]
122433316  TSC2; tuberin isoform X1 [KO:K07207]
122438889  RHEB; GTP-binding protein Rheb [KO:K07208]
122452383  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122446193  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]
122446493  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
122447376  CCNA1; cyclin-A1 [KO:K06627]
122422114  CCNA2; cyclin-A2 [KO:K06627]
122448311  MYBL2; myb-related protein B isoform X1 [KO:K21769]
122452260  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
122421440  LIN37; protein lin-37 homolog isoform X1 [KO:K21774]
122443849  LIN52; protein lin-52 homolog isoform X1 [KO:K21775]
122428076  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
122426108  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
122453278  LOW QUALITY PROTEIN: histone-binding protein RBBP4-like [KO:K10752]
122423676  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
122451212  MYC; myc proto-oncogene protein [KO:K04377]
122452871  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
122427080  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
122445826  TP53; cellular tumor antigen P53 [KO:K04451]
122451811  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
122454491  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
122446012  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
122438712  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
122421749  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
122449505  HIPK3; homeodomain-interacting protein kinase 3 isoform X1 [KO:K08826] [EC:2.7.11.1]
122436028  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
122440096  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
122430818  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
122441910  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
122423576  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
122435753  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
122425059  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122443062  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122440231  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122440910  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122446062  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122447261  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
122433033  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122455309  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122431322  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
122443696  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
122429019  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
122429123  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
122429963  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
122423531  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
122423529  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
122440181  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122432031  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122436847  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122446536  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
122434837  G2/mitotic-specific cyclin-B1-like [KO:K05868]
122454476  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
122443546  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
122435261  CCNB3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
122449987  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
122440152  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
122450863  NBN; nibrin isoform X1 [KO:K10867]
122450584  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
122421545  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
122430819  RAD9A; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
122423629  RAD9B; cell cycle checkpoint control protein RAD9B isoform X1 [KO:K10995]
122454333  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
122438504  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
122445242  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
122430784  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
122424249  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
122440582  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
122453285  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
122422914  TRAF3IP2; E3 ubiquitin ligase TRAF3IP2 isoform X1 [KO:K21124]
122422050  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122430633  RELA; transcription factor p65 isoform X1 [KO:K04735]
122442617  IL1A; interleukin-1 alpha [KO:K04383]
122438196  IL6; interleukin-6 [KO:K05405]
122428451  CXCL8; interleukin-8 [KO:K10030]
122428482  C-X-C motif chemokine 15-like isoform X1 [KO:K10030]
122438512  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
122433325  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
122432485  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
122441621  ZFP36L2; mRNA decay activator protein ZFP36L2 [KO:K18753]
122443789  ZFP36L1; mRNA decay activator protein ZFP36L1 [KO:K18753]
122435446  LOW QUALITY PROTEIN: mRNA decay activator protein ZFP36L2-like [KO:K18753]
122424654  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
122422291  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
122443614  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
122430944  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
122435630  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
122452395  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
122420755  CALM3; calmodulin-3 [KO:K02183]
122420753  calmodulin-1-like [KO:K02183]
122448900  calmodulin-2/4-like [KO:K02183]
122448285  calmodulin-like [KO:K02183]
122441648  CALM2; calmodulin-2 [KO:K02183]
122453208  calmodulin-1-like [KO:K02183]
122443081  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
122451732  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
122443955  CALM1; calmodulin-1 isoform X1 [KO:K02183]
122445547  calmodulin-1 [KO:K02183]
122422203  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
122431708  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
122446399  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
122431959  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
122441856  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
122425388  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
122448615  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
122420851  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
122443145  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
122424343  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
122423671  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
122430147  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
122432310  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
122434361  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
122455040  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
122435311  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
122453523  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
122439923  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
122446361  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
122432435  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
122446414  MCU; 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
ccad04020  Calcium signaling pathway
ccad04068  FoxO signaling pathway
ccad04110  Cell cycle
ccad04115  p53 signaling pathway
ccad04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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