KEGG   PATHWAY: pss04218
Entry
pss04218                    Pathway                                
Name
Cellular senescence - Pelodiscus sinensis (Chinese soft-shelled 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
pss04218  Cellular senescence
pss04218

Other DBs
GO: 0090398
Organism
Pelodiscus sinensis (Chinese soft-shelled turtle) [GN:pss]
Gene
102452874  TGFB2; transforming growth factor beta-2 [KO:K13376]
102456369  TGFB3; transforming growth factor beta-3 [KO:K13377]
102444710  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102457599  TGF-beta receptor type-2-like isoform X1 [KO:K04388] [EC:2.7.11.30]
102457921  SMAD2; mothers against decapentaplegic homolog 2 isoform X2 [KO:K04500]
102449871  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
102449535  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
102450272  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
102454031  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102457993  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102462674  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102445982  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
102445665  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102459602  RBL1; retinoblastoma-like protein 1 [KO:K04681]
102445416  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102448890  E2F1; transcription factor E2F1 [KO:K17454]
102453459  E2F2; transcription factor E2F2 [KO:K09389]
102446755  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102450367  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
102456799  E2F4; transcription factor E2F4 [KO:K04682]
102459577  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102462482  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
102448624  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102461096  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102457516  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102449585  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102449767  FOXO1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
102455970  FOXO3; forkhead box protein O3 [KO:K09408]
102450716  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102453637  cyclin-dependent kinase inhibitor 1-like isoform X1 [KO:K06625]
102459974  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102460990  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
102445271  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
102446305  LOW QUALITY PROTEIN: class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
102452322  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
102446295  class I histocompatibility antigen, F10 alpha chain [KO:K06751]
102447251  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
102450646  KRAS; GTPase KRas isoform X1 [KO:K07827]
102447991  NRAS; GTPase NRas [KO:K07828]
102448013  RRAS2; ras-related protein R-Ras2 [KO:K07830]
102449741  MRAS; ras-related protein M-Ras isoform X2 [KO:K07831]
102457627  HRAS; GTPase HRas isoform X2 [KO:K02833]
102453850  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102448379  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102453047  TSC1; hamartin isoform X2 [KO:K07206]
102448020  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
102461522  RHEB; GTP-binding protein Rheb isoform X1 [KO:K07208]
102451030  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
102443573  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]
102446525  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
102450157  CCNA1; cyclin-A1 isoform X3 [KO:K06627]
102444384  CCNA2; cyclin-A2 [KO:K06627]
102462523  MYBL2; myb-related protein B isoform X5 [KO:K21769]
102459629  LIN9; protein lin-9 homolog isoform X1 [KO:K21773]
102448069  LIN37; protein lin-37 homolog [KO:K21774]
102447245  LIN52; protein lin-52 homolog [KO:K21775]
102445758  LIN54; protein lin-54 homolog isoform X1 [KO:K21776]
102443802  RBBP4; histone-binding protein RBBP4 isoform X1 [KO:K10752]
102457620  FOXM1; forkhead box protein M1 [KO:K09406]
102449445  MYC; myc proto-oncogene protein [KO:K04377]
102447336  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102448135  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
102445044  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
102460007  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
102449762  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
102446035  HIPK1; homeodomain-interacting protein kinase 1 isoform X1 [KO:K08826] [EC:2.7.11.1]
102461921  HIPK3; homeodomain-interacting protein kinase 3 [KO:K08826] [EC:2.7.11.1]
102461700  HIPK2; homeodomain-interacting protein kinase 2 isoform X1 [KO:K08826] [EC:2.7.11.1]
102459862  HIPK4; homeodomain-interacting protein kinase 4 [KO:K08826] [EC:2.7.11.1]
102463789  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102463695  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102450584  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102449920  serine/threonine-protein phosphatase PP1-gamma catalytic subunit B [KO:K06269] [EC:3.1.3.16]
102458748  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102443595  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102457075  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102453948  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102446243  ETS1; protein C-ets-1 isoform X1 [KO:K02678]
102454019  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102461243  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102455939  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102462429  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102462672  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
102448785  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102457123  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102447859  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102460773  growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402]
102448219  CDK1; cyclin-dependent kinase 1 isoform X2 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102448879  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
102454875  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102451303  MRE11; double-strand break repair protein MRE11 isoform X1 [KO:K10865]
102447517  RAD50; DNA repair protein RAD50 [KO:K10866] [EC:3.6.-.-]
102451272  NBN; nibrin isoform X2 [KO:K10867]
102462597  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
102461937  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
102463200  RAD9A; cell cycle checkpoint control protein RAD9A [KO:K10994] [EC:3.1.11.2]
102450111  RAD9B; cell cycle checkpoint control protein RAD9B [KO:K10995]
102449276  RAD1; cell cycle checkpoint protein RAD1 [KO:K02830] [EC:3.1.11.2]
102445937  HUS1; checkpoint protein HUS1 isoform X1 [KO:K10903]
102459396  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102451245  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102458852  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
102457855  SQSTM1; sequestosome-1 [KO:K14381]
102452046  GATA4; transcription factor GATA-4 [KO:K09183]
102463637  TRAF3IP2; adapter protein CIKS isoform X1 [KO:K21124]
102457132  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
102457804  RELA; transcription factor p65 isoform X1 [KO:K04735]
102450313  IL6; interleukin-6 [KO:K05405]
102453911  interleukin-8-like [KO:K10030]
102454632  interleukin-8-like [KO:K10030]
102454894  interleukin-8-like [KO:K10030]
102454150  interleukin-8 isoform X1 [KO:K10030]
102445995  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
102443480  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
102459901  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102445709  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102452922  ZFP36L1; mRNA decay activator protein ZFP36L1 isoform X2 [KO:K18753]
102460767  ZFP36; mRNA decay activator protein ZFP36 [KO:K18753]
102447276  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102444313  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102461295  transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102458417  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102448184  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
102458713  CAPN2; LOW QUALITY PROTEIN: calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102459065  CALML3; calmodulin-like protein 3 [KO:K02183]
102462006  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
102462265  CALM1; calmodulin-1 [KO:K02183]
102454393  calmodulin-like [KO:K02183]
102452499  calmodulin isoform X2 [KO:K02183]
102458420  neo-calmodulin-like [KO:K02183]
102456219  calmodulin-A-like isoform X1 [KO:K02183]
102456795  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102452008  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102445775  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102453558  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102457798  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102448775  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
102452242  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102463175  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102447163  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
102462538  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
102453428  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102449833  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102446093  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102461807  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102444939  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
102458327  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102456377  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
102447058  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102450498  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102450215  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
102451453  MCU; LOW QUALITY PROTEIN: 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
pss04020  Calcium signaling pathway
pss04068  FoxO signaling pathway
pss04110  Cell cycle
pss04115  p53 signaling pathway
pss04150  mTOR signaling pathway
KO pathway
ko04218   
LinkDB

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