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Gene Review

tp53  -  tumor protein p53

Danio rerio

Synonyms: Cellular tumor antigen p53, SO:0000704, Tumor suppressor p53, brp53, drp53, ...
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Disease relevance of tp53


High impact information on tp53

  • A loss-of-function mutation in def confers hypoplastic digestive organs and selectively up-regulates the expression of Delta113p53, counterpart to a newly identified isoform of p53 produced by an alternative internal promoter in intron 4 of the p53 gene in human [3].
  • However, there is currently no direct genetic evidence to show if or how the p53 pathway functions during organogenesis [3].
  • In addition to providing a model for studying the molecular pathogenic pathways of malignant peripheral nerve sheath tumors, these mutant zebrafish lines provide a unique platform for modifier screens to identify genetic mutations or small molecules that affect tp53-related pathways, including apoptosis, cell-cycle delay, and tumor suppression [1].
  • Zebrafish lines harboring missense mutations in the tp53 DNA-binding domain were identified by using a target-selected mutagenesis strategy [1].
  • Ectopic expression of these basic helix-loop-helix transcription factors in both zebrafish and avian developmental systems activated p53 and induced apoptosis in vivo, resulting in a phenotype similar to that of p53 overexpression [4].

Biological context of tp53

  • Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss [5].
  • This indicates that under replication-compromised conditions, the p53 branch of the S-phase checkpoint is responsible for eliminating stalled cells that, given more time, would have otherwise finished their normal developmental program [6].
  • In addition, it contributes to p53-dependent and UV-induced cell death [7].
  • These different effects are supposed to be mediated by the transcriptional activation of different target genes. perp, encoding a transmembrane protein of the Pmp22 family, is a transcriptional p53 target exclusively upregulated in apoptotic cells [7].
  • p53, p63 and p73 are related transcription factors involved in the regulation of cell proliferation, survival and differentiation [8].

Anatomical context of tp53

  • Expression of zebrafish p73 mRNA is restricted to tissues such as skin, fin, brain, ovary, and testis, in contrast to the ubiquitous expression of zebrafish p53 and p63 [9].
  • Northern analysis demonstrated a zebrafish p53-related transcript to be present and most abundant in zygotes and early-cleavage embryos less than 1 hour after fertilization, thereafter declining to barely detectable levels at 48 hours [10].
  • Furthermore, ras- and myc-mediated transformation of mouse embryonic fibroblasts was abrogated by expression of HEY1 in a p53-dependent manner [4].

Associations of tp53 with chemical compounds


Other interactions of tp53

  • Our results demonstrate that knockdown of Pen-2 directly induces a p53-dependent apoptotic pathway that contributes to neuronal loss and suggest that Pen-2 plays an important role in promoting neuronal cell survival and protecting from apoptosis in vivo [5].
  • This YSL targeting is p53 sequence-specific because GFP fusion proteins of p63 and p73 displayed neuronal-specific patterns [12].
  • However, during normal zebrafish development, perp displays a p53-independent and spatially restricted expression in specific cell types and tissues [7].

Analytical, diagnostic and therapeutic context of tp53


  1. tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Berghmans, S., Murphey, R.D., Wienholds, E., Neuberg, D., Kutok, J.L., Fletcher, C.D., Morris, J.P., Liu, T.X., Schulte-Merker, S., Kanki, J.P., Plasterk, R., Zon, L.I., Look, A.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Stem-cell leukemia: p53 deficiency mediated suppression of leukemic differentiation in C3H/He myeloid leukemia. Yoshida, K., Aizawa, S., Watanabe, K., Hirabayashi, Y., Inoue, T. Leuk. Res. (2002) [Pubmed]
  3. Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish. Chen, J., Ruan, H., Ng, S.M., Gao, C., Soo, H.M., Wu, W., Zhang, Z., Wen, Z., Lane, D.P., Peng, J. Genes Dev. (2005) [Pubmed]
  4. Identification of p53 regulators by genome-wide functional analysis. Huang, Q., Raya, A., DeJesus, P., Chao, S.H., Quon, K.C., Caldwell, J.S., Chanda, S.K., Izpisua-Belmonte, J.C., Schultz, P.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss. Campbell, W.A., Yang, H., Zetterberg, H., Baulac, S., Sears, J.A., Liu, T., Wong, S.T., Zhong, T.P., Xia, W. J. Neurochem. (2006) [Pubmed]
  6. p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase delta1. Plaster, N., Sonntag, C., Busse, C.E., Hammerschmidt, M. Cell Death Differ. (2006) [Pubmed]
  7. Perp is required for tissue-specific cell survival during zebrafish development. Nowak, M., Köster, C., Hammerschmidt, M. Cell Death Differ. (2005) [Pubmed]
  8. Specific and conserved roles of TAp73 during zebrafish development. Rentzsch, F., Kramer, C., Hammerschmidt, M. Gene (2003) [Pubmed]
  9. Cloning and developmental expression of p73 cDNA in zebrafish. Pan, H., Dung, H.N., Hsu, H.M., Hsiao, K.M., Chen, L.Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  10. Zebrafish (Danio rerio) p53 tumor suppressor gene: cDNA sequence and expression during embryogenesis. Cheng, R., Ford, B.L., O'Neal, P.E., Mathews, C.Z., Bradford, C.S., Thongtan, T., Barnes, D.W., Hendricks, J.D., Bailey, G.S. Mol. Marine Biol. Biotechnol. (1997) [Pubmed]
  11. Pentachlorophenol treatment in vivo elevates point mutation rate in zebrafish p53 gene. Yin, D., Gu, Y., Li, Y., Wang, X., Zhao, Q. Mutat. Res. (2006) [Pubmed]
  12. Requirement of nuclear localization and transcriptional activity of p53 for its targeting to the yolk syncytial layer (YSL) nuclei in zebrafish embryo and its use for apoptosis assay. Chen, G.D., Chou, C.M., Hwang, S.P., Wang, F.F., Chen, Y.C., Hung, C.C., Chen, J.Y., Huang, C.J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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