KEGG   PATHWAY: asn04218
Entry
asn04218                    Pathway                                
Name
Cellular senescence - Alligator sinensis (Chinese alligator)
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
asn04218  Cellular senescence
asn04218

Other DBs
GO: 0090398
Organism
Alligator sinensis (Chinese alligator) [GN:asn]
Gene
102369002  TGFB1; transforming growth factor beta-1 [KO:K13375]
102382227  TGFB2; transforming growth factor beta-2 [KO:K13376]
102384560  TGFB3; transforming growth factor beta-3 [KO:K13377]
102370778  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
102380434  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102371879  LOW QUALITY PROTEIN: TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
102370509  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102379863  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102387479  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102387975  CDK6; cyclin-dependent kinase 6 isoform X2 [KO:K02091] [EC:2.7.11.22]
102378816  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102386423  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102379703  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102379720  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102372889  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
102379028  E2F1; transcription factor E2F1 [KO:K17454]
102375233  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102387519  E2F3; transcription factor E2F3 [KO:K06620]
102378682  E2F5; transcription factor E2F5 [KO:K04682]
102381316  E2F4; transcription factor E2F4 [KO:K04682]
102388304  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102372482  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102387818  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102382060  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102377899  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102380057  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102388853  FOXO1; forkhead box protein O1 [KO:K07201]
102373584  FOXO3; forkhead box protein O3 [KO:K09408]
102368723  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06625]
102379358  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102376317  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102368597  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102382034  CCNE1; LOW QUALITY PROTEIN: G1/S-specific cyclin-E1 [KO:K06626]
102367803  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102378986  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102379493  H-2 class I histocompatibility antigen, Q9 alpha chain-like isoform X1 [KO:K06751]
102368919  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102384475  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
102382365  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102385058  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102382206  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102375088  major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751]
102368503  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102378561  class I histocompatibility antigen, F10 alpha chain-like isoform X1 [KO:K06751]
102379232  major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751]
102388210  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102388710  major histocompatibility complex class I-related gene protein-like [KO:K06751]
102380209  class I histocompatibility antigen, F10 alpha chain [KO:K06751]
102386566  major histocompatibility complex class I-related gene protein-like [KO:K06751]
112547860  GTPase HRas-like [KO:K07827]
102373235  KRAS; GTPase KRas [KO:K07827]
102382019  NRAS; GTPase NRas [KO:K07828]
102371276  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
102381265  RRAS; ras-related protein R-Ras isoform X2 [KO:K07830]
102376534  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
102380807  HRAS; GTPase HRas [KO:K02833]
102388514  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
102388207  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102372104  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102383470  TSC1; LOW QUALITY PROTEIN: hamartin [KO:K07206]
102387523  TSC2; tuberin isoform X1 [KO:K07207]
102381385  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
102372197  MTOR; serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
106721809  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102369643  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
102388230  CCNA2; cyclin-A2 [KO:K06627]
102377779  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
102368128  MYBL2; myb-related protein B isoform X1 [KO:K21769]
102387566  LIN9; protein lin-9 homolog isoform X2 [KO:K21773]
102379872  LIN37; protein lin-37 homolog [KO:K21774]
102385082  LIN54; protein lin-54 homolog isoform X2 [KO:K21776]
102369710  RBBP4; histone-binding protein RBBP4 isoform X2 [KO:K10752]
102387724  FOXM1; forkhead box protein M1 isoform X1 [KO:K09406]
102370393  MYC; myc proto-oncogene protein [KO:K04377]
102385768  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102376594  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
102383946  RASSF5; LOW QUALITY PROTEIN: ras association domain-containing protein 5 [KO:K08015]
102370841  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
102381867  F-box/WD repeat-containing protein 1A [KO:K03362]
102376526  HIPK2; homeodomain-interacting protein kinase 2 isoform X3 [KO:K08826] [EC:2.7.11.1]
102382671  HIPK3; homeodomain-interacting protein kinase 3 isoform X2 [KO:K08826] [EC:2.7.11.1]
102383402  HIPK1; LOW QUALITY PROTEIN: homeodomain-interacting protein kinase 1 [KO:K08826] [EC:2.7.11.1]
102375415  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102373171  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102383008  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
102374398  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102373880  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102375508  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102376690  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102375250  glycogen synthase kinase-3 alpha-like [KO:K04371] [EC:2.7.11.24]
102381885  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
102383945  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102373782  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
102374196  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102375954  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102376541  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102375835  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102374205  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102372381  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102374172  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102385352  CDK1; LOW QUALITY PROTEIN: cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102381467  CCNB1; G2/mitotic-specific cyclin-B1 isoform X2 [KO:K05868]
102376865  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102373322  CCNB3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
102388581  MRE11; double-strand break repair protein MRE11 [KO:K10865]
102372882  RAD50; DNA repair protein RAD50 isoform X1 [KO:K10866] [EC:3.6.-.-]
102380627  NBN; nibrin isoform X1 [KO:K10867]
102387373  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102386466  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
102369329  RAD9A; cell cycle checkpoint control protein RAD9A isoform X1 [KO:K10994] [EC:3.1.11.2]
102376415  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
102376989  RAD1; cell cycle checkpoint protein RAD1 isoform X1 [KO:K02830] [EC:3.1.11.2]
102386730  checkpoint protein HUS1-like [KO:K10903]
102378578  HUS1; LOW QUALITY PROTEIN: checkpoint protein HUS1 [KO:K10903]
102377502  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
102385348  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102384816  CDC25A; LOW QUALITY PROTEIN: M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
102373404  SQSTM1; sequestosome-1 isoform X2 [KO:K14381]
102371754  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
102384842  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
102369946  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102377458  RELA; transcription factor p65 [KO:K04735]
102377828  IL6; interleukin-6 [KO:K05405]
102374630  interleukin-8-like [KO:K10030]
102374877  interleukin-8-like [KO:K10030]
102375355  interleukin-8-like [KO:K10030]
102375115  interleukin-8-like [KO:K10030]
102372891  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
102369661  plasminogen activator inhibitor 1 [KO:K03982]
102383452  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102382484  ZFP36L1; mRNA decay activator protein ZFP36L1 isoform X1 [KO:K18753]
102373960  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102383407  TRPV4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102372173  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102368421  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
102375021  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102373508  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102369688  calmodulin-alpha-like [KO:K02183]
102374592  CALM3; calmodulin-3 [KO:K02183]
102369607  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
102373272  CALM2; calmodulin-2 [KO:K02183]
102381160  CALM1; calmodulin-1 [KO:K02183]
102381186  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102386011  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102377124  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102382032  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102377091  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102386486  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102375111  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102375265  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
102385401  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
102379206  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
102379727  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102381395  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102371094  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102384953  ADP/ATP translocase 3 [KO:K05863]
102376128  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102387986  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102380636  PPID; peptidyl-prolyl cis-trans isomerase D isoform X1 [KO:K05864] [EC:5.2.1.8]
102383593  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
102381104  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
102370144  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
102378241  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
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
asn04020  Calcium signaling pathway
asn04068  FoxO signaling pathway
asn04110  Cell cycle
asn04115  p53 signaling pathway
asn04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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