KEGG   PATHWAY: dre04115
Entry
dre04115                    Pathway                                
Name
p53 signaling pathway - Danio rerio (zebrafish)
Description
p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways.
Class
Cellular Processes; Cell growth and death
Pathway map
dre04115  p53 signaling pathway
dre04115

Organism
Danio rerio (zebrafish) [GN:dre]
Gene
403064  atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
336998  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
567770  atr; serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
393162  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
393356  gorab; RAB6-interacting golgin isoform 1 [KO:K19748]
30637  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform 1 [KO:K06643] [EC:2.3.2.27]
334932  mdm4; protein Mdm4 isoform 1 [KO:K10127]
30590  tp53; cellular tumor antigen p53 isoform 2 [KO:K04451]
541507  ppp1r13l; relA-associated inhibitor [KO:K27356]
100151416  cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100151464  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
30222  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
799608  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
565038  ccnd2b; G1/S-specific cyclin-D2b [KO:K10151]
449996  ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
777730  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100034507  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
569515  cdk21; cyclin-dependent kinase 6-like [KO:K02091] [EC:2.7.11.22]
415165  ccne2; G1/S-specific cyclin-E2 [KO:K06626]
30188  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
406715  cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
553689  rprma; protein reprimo A [KO:K10128]
393779  rprmb; protein reprimo B [KO:K10128]
436699  rprm3; reprimo, TP53 dependent G2 arrest mediator homolog 3 [KO:K10128]
58025  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
447870  ccnb1l; cyclin B1, like [KO:K05868]
368316  ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
80973  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
393548  gadd45aa; growth arrest and DNA-damage-inducible, alpha, a [KO:K04402]
402991  gadd45ga; growth arrest and DNA-damage-inducible, gamma a [KO:K04402]
431763  gadd45ab; growth arrest and DNA-damage-inducible, alpha, b [KO:K04402]
406304  gadd45ba; growth arrest and DNA-damage-inducible, beta a [KO:K04402]
497646  gadd45bb; growth arrest and DNA-damage-inducible, beta b [KO:K04402]
406507  gadd45gb.1; growth arrest and DNA-damage-inducible, gamma b, tandem duplicate 1 [KO:K04402]
553652  gtse1; G2 and S phase-expressed protein 1 [KO:K10129]
100147851  znf385a; zinc finger protein 385A isoform X1 [KO:K26543]
768248  fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
571033  pidd1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
373093  hdr; hematopoietic death receptor precursor [KO:K04722]
58022  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
557302  casp8l2; caspase-8 [KO:K04398] [EC:3.4.22.61]
561021  casp22; caspase-22 [KO:K04398] [EC:3.4.22.61]
100049706  casp8l1; caspase 8, apoptosis-related cysteine peptidase, like 1 [KO:K04398] [EC:3.4.22.61]
559425  bida; BH3 interacting domain death agonist [KO:K04726]
58081  baxa; BCL2 associated X, apoptosis regulator a [KO:K02159]
100004321  apoptosis regulator BAX-like [KO:K02159]
767645  zgc:153993; uncharacterized protein LOC767645 [KO:K02159]
751765  pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
571845  siva1; apoptosis regulatory protein Siva [KO:K22744]
114401  bcl2l1; bcl-2-like protein 1 [KO:K04570]
100007048  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
570772  bcl2a; apoptosis regulator Bcl-2a [KO:K02161]
796473  tp53i3; quinone oxidoreductase PIG3 isoform X2 [KO:K10133] [EC:1.-.-.-]
550597  ei24; etoposide-induced protein 2.4 homolog [KO:K10134]
558619  shisa10.1; uncharacterized protein LOC558619 precursor [KO:K10135]
494479  perp; p53 apoptosis effector related to PMP-22 [KO:K10136]
561535  zmat3; zinc finger matrin-type protein 3 [KO:K10137]
80955  siah1; E3 ubiquitin-protein ligase Siah1 [KO:K04506] [EC:2.3.2.27]
415158  cycsb; cytochrome c [KO:K08738]
58131  apaf1; apoptotic protease-activating factor 1 [KO:K02084]
492763  casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
140621  casp3a; caspase-3a [KO:K02187] [EC:3.4.22.56]
566604  casp3b; caspase-3b [KO:K02187] [EC:3.4.22.56]
557507  aifm2; apoptosis-inducing factor 2 [KO:K22745]
403079  igfbp3; insulin-like growth factor-binding protein 3 precursor [KO:K10138]
114433  igf1; insulin-like growth factor I precursor [KO:K05459]
100136840  serpine1; plasminogen activator inhibitor 1 precursor [KO:K03982]
563527  adgrb1a; brain-specific angiogenesis inhibitor 1 isoform X1 [KO:K04596]
324098  cd82a; CD82 molecule a [KO:K06509]
324137  cd82b; CD82 molecule b [KO:K06509]
561901  thbs1b; thrombospondin-1 isoform X1 [KO:K16857]
100332237  thbs1a; thrombospondin-1 [KO:K16857]
100004133  ddb2; DNA damage-binding protein 2 [KO:K10140]
30733  rrm2; ribonucleoside-diphosphate reductase subunit M2 [KO:K10808] [EC:1.17.4.1]
100330864  ribonucleoside-diphosphate reductase subunit M2 isoform 1 [KO:K10808] [EC:1.17.4.1]
368909  rrm2b; ribonucleoside-diphosphate reductase subunit M2 B [KO:K10808] [EC:1.17.4.1]
436933  sesn1; sestrin-1 [KO:K10141]
406840  sesn3; sestrin-3 [KO:K10141]
100149048  si:zfos-80g12.1; sestrin-3-like [KO:K10141]
100149745  sesn2; sestrin-2 [KO:K20394]
368415  ptenb; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform 2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
794088  ptena; phosphatase and tensin homolog A [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
567524  tsc2; tuberin [KO:K07207]
100320152  steap3; metalloreductase STEAP3 [KO:K10142] [EC:1.16.1.-]
100037391  cop1; E3 ubiquitin-protein ligase COP1 [KO:K10143] [EC:2.3.2.27]
321875  rchy1; RING finger and CHY zinc finger domain-containing protein 1 [KO:K10144] [EC:2.3.2.27]
171473  ccng1; cyclin-G1 [KO:K10145]
266794  ccng2; cyclin-G2 [KO:K10146]
492468  ppm1db; protein phosphatase, Mg2+/Mn2+ dependent, 1Db [KO:K10147] [EC:3.1.3.16]
394065  ppm1da; protein phosphatase, Mg2+/Mn2+ dependent, 1Da [KO:K10147] [EC:3.1.3.16]
368221  tp73; tumor protein p73 [KO:K10148]
Reference
PMID:16557269
  Authors
Levine AJ, Hu W, Feng Z.
  Title
The P53 pathway: what questions remain to be explored?
  Journal
Cell Death Differ 13:1027-36 (2006)
DOI:10.1038/sj.cdd.4401910
Reference
PMID:15838523
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11747320
  Authors
Balint E E, Vousden KH.
  Title
Activation and activities of the p53 tumour suppressor protein.
  Journal
Br J Cancer 85:1813-23 (2001)
DOI:10.1054/bjoc.2001.2128
Reference
PMID:11313928
  Authors
Taylor WR, Stark GR.
  Title
Regulation of the G2/M transition by p53.
  Journal
Oncogene 20:1803-15 (2001)
DOI:10.1038/sj.onc.1204252
Reference
PMID:15116721
  Authors
Hofseth LJ, Hussain SP, Harris CC.
  Title
p53: 25 years after its discovery.
  Journal
Trends Pharmacol Sci 25:177-81 (2004)
DOI:10.1016/j.tips.2004.02.009
Reference
PMID:12505356
  Authors
Pietenpol JA, Stewart ZA.
  Title
Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis.
  Journal
Toxicology 181-182:475-81 (2002)
DOI:10.1016/S0300-483X(02)00460-2
Reference
PMID:10714958
  Authors
Tokino T, Nakamura Y.
  Title
The role of p53-target genes in human cancer.
  Journal
Crit Rev Oncol Hematol 33:1-6 (2000)
DOI:10.1016/S1040-8428(99)00051-7
Reference
PMID:16697662
  Authors
Hermeking H, Benzinger A.
  Title
14-3-3 proteins in cell cycle regulation.
  Journal
Semin Cancer Biol 16:183-92 (2006)
DOI:10.1016/j.semcancer.2006.03.002
Reference
PMID:16915296
  Authors
Sherr CJ.
  Title
Divorcing ARF and p53: an unsettled case.
  Journal
Nat Rev Cancer 6:663-73 (2006)
DOI:10.1038/nrc1954
Reference
PMID:17409411
  Authors
Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ.
  Title
The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways.
  Journal
Cancer Res 67:3043-53 (2007)
DOI:10.1158/0008-5472.CAN-06-4149
Reference
PMID:26037915
  Authors
Resnick-Silverman L, Manfredi JJ
  Title
Two Faces of SIVA.
  Journal
Cancer Discov 5:581-3 (2015)
DOI:10.1158/2159-8290.CD-15-0484
Reference
PMID:19584092
  Authors
Resch U, Schichl YM, Winsauer G, Gudi R, Prasad K, de Martin R
  Title
Siva1 is a XIAP-interacting protein that balances NFkappaB and JNK signalling to promote apoptosis.
  Journal
J Cell Sci 122:2651-61 (2009)
DOI:10.1242/jcs.049940
Reference
PMID:19240372
  Authors
Barkinge JL, Gudi R, Sarah H, Chu F, Borthakur A, Prabhakar BS, Prasad KV
  Title
The p53-induced Siva-1 plays a significant role in cisplatin-mediated apoptosis.
  Journal
J Carcinog 8:2 (2009)
DOI:10.4103/1477-3163.45389
Reference
PMID:12135761
  Authors
Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N
  Title
A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).
  Journal
FEBS Lett 524:163-71 (2002)
DOI:10.1016/S0014-5793(02)03049-1
Reference
PMID:26646590
  Authors
Hu Y, Ge W, Wang X, Sutendra G, Zhao K, Dedeic Z, Slee EA, Baer C, Lu X
  Title
Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-kappaB.
  Journal
Oncotarget 6:42478-90 (2015)
DOI:10.18632/oncotarget.6478
Related
pathway
dre04110  Cell cycle
dre04210  Apoptosis
dre04218  Cellular senescence
KO pathway
ko04115   
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