Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens

다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰

  • 정화진 (경희대학교 의과대학 약리학 교실 및 MRC 센터) ;
  • 류재천 (한국과학기술연구원 독성학실험실) ;
  • 서영록 (경희대학교 의과대학 약리학 교실 및 MRC 센터)
  • Published : 2004.09.01
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Abstract

The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

Keywords

References

  1. Appella E and Anderson CW. Signaling to p53: breaking the posttranslational modification code, Pathol. Biol. (Paris) 2000; 48: 227-245
  2. Bartek J, Vojtesek B and Lane DP. Diversity of human p53 mutants revealed by complex formation to SV40 T antigen, Eur. J. Cancer 1992; 29: 101-107 https://doi.org/10.1016/0959-8049(93)90584-3
  3. Bell S, Klein C, Muller L, Hansen S and Buchner J. p53 contains large unstructured regions in its native state, J. Mol. Biol. 2002; 322: 917-927 https://doi.org/10.1016/S0022-2836(02)00848-3
  4. Cistulli CA and K.aufman WK. p53-dependent signalling sustains DNA replication and enhances clonogenic survival in 254nm ultraviolet-irradiated human fibro-blasts, Cancer Res. 1998; 58: 1993-2002
  5. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS and Bradley A. Mice deficient for p53 are developmentally normal but suscep-tible to spontaneous tumours, Nature 1992; 356: 215-221 https://doi.org/10.1038/356215a0
  6. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B. WAFl, a potential mediator of p53 tumor suppression, Cell 1993; 75: 817-825 https://doi.org/10.1016/0092-8674(93)90500-P
  7. Ford JM and Hanawalt PC. Expression of wild-type p53 is required for efficient global genomic nucleotide excision repair in UV-resistance, Proc. Natl. Acad. Sci. USA 1997; 92: 8876-8880 https://doi.org/10.1073/pnas.92.19.8876
  8. Fritsche M, Haessler C and Brandner G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents, Oncogene 1993; 8: 307-318
  9. Graeber TG, Peterson JF, Tsai M, Monica K, Fomace AJ Jr and Giaccia AJ. Hypoxia induces accumulation of p53 protein, but activation of a Gl-phase checkpoint by low-oxygen conditions is independent of p53 status, Mol. Cell Biol. 1994; 14: 6264-6277 https://doi.org/10.1128/MCB.14.9.6264
  10. Hollstein M, Rice K, Greenblatt MS, Sussi T, Fuchs R, Sorlie T, Hovig E, Smith-Sorensen B, Montesano R and Harris CC. Database of p53 gene somatic mutations in human tumors and cell lines, Nucleic Acids Res. 1994; 22: 3551-3555
  11. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B and Craig RW. Participation of p53 protein in the cellular resonse to DNA damage, Cancer Res. 1991; 51: 6304-6311
  12. Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace AJ Jr. A mammalian cell cycle checkpoint pathway utiliz-ing p53 and GADD45 is defective in ataxia-telangiec-tasia, Cell 1992; 71: 587-597 https://doi.org/10.1016/0092-8674(92)90593-2
  13. Lane DP. Cancer. p53, guardian of the genome, Nature 1992; 358: 15-16 https://doi.org/10.1038/358015a0
  14. Levine AJ. p53, the cellular gatekeeper for growth and division, Cell 1997; 88: 323-331 https://doi.org/10.1016/S0092-8674(00)81871-1
  15. Malkin D. p53 and the Li-Fraumeni syndrome, Biochim. Biophys. Acta 1994; 1198: 197-213
  16. Marshall HE, Merchant K and Stamter JS. Nitrosation and oxidation in the regulation of gene expression, FASEBJ. 2000;14:1889-1900 https://doi.org/10.1096/fj.00.011rev
  17. Meplan C, Richard MJ and Hainaut P. Redox signalling and transition metals in the control of the p53 pathway, Biol. Pharmacol. 2000; 59: 25-33
  18. Oliver M, Eeles R, Hollstein M, Khan MA, Harris CC and Hainaut P. The IARC TP53 Database: new online mutation analysis and recommendations to users, Hum Mutat 2002; 19: 607-614 https://doi.org/10.1002/humu.10081
  19. Rodrigues NR, Rowan A, Smith MEF, Kerr IB, Bodmer WF, Gannon JV and Lane DP. p53 mutations in col-orectal cancer, Proc. Natl. Acad. Sci. USA 1990; 87: 7555-7559 https://doi.org/10.1073/pnas.87.19.7555
  20. Ryan KM, Phillips AC and Vousden KH. Regulation and function of the p53 tumor suppressor protein, Curr. Opin. Cell. Biol. 2001; 13: 332-337 https://doi.org/10.1016/S0955-0674(00)00216-7
  21. Schuler M, Bossy-Wetzel E, Goldstein JC, Fitzgerald P and Green DR. p53 induces apoptosis by caspase activation through rnitochondrial cytochrome c release, J. Biol. Chem. 2000; 275: 7337-7342 https://doi.org/10.1074/jbc.275.10.7337
  22. Seo YR, Fishel ML, Amundson S, Kelley MR and Smith ML. Implication of p53 in base excision DNA repair: in vivo evidence, Oncogene 2002; 21: 731-737 https://doi.org/10.1038/sj.onc.1205129
  23. Seo YR, Kelley MR and Smith ML. Selenomethionine regu-lation of p53 by a refl-dependent redox mechanism, Proc. Natl. Acad. Sci. USA 2002; 99: 14548-14553 https://doi.org/10.1073/pnas.212319799
  24. Shaw P, Bovey R, Tardy S, Sahli R, Sordat B and Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line, Proc. Natl. Sci. USA 1992; 89: 4495-4499 https://doi.org/10.1073/pnas.89.10.4495
  25. Sheikh MS and Fornace AJ Jr. Death and decoy receptors and p53-mediated apoptosis, Leukemia 2000; 14: 1509-1513 https://doi.org/10.1038/sj.leu.2401865
  26. Smith ML, Ford JM, Hollander C, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC and Fornace AJ Jr. p53-mediated DNA repair responses to UV radiation: Studies of mouse cells lacking p53, p21, and/or gadd45 genes, Mol. and cellular biol. 2000; 20: 3705-3714 https://doi.org/10.1128/MCB.20.10.3705-3714.2000
  27. Starzynska T. Protein p53 in gastric carcinoma: clinical use of cancer research on neoplasms, Pol. Merkunusz Lek. 1999; 6: 61-64
  28. Yin Y, Terauchi Y, Solomon GG, Aizawa S, Rangarajan PN, Yazaki Y, Kadowaki T and Barrett JC. Involvement of p85 in p53-dependent apoptotic response to oxida-tive stress, Nature 1998, 391: 707-710 https://doi.org/10.1038/35648
  29. Yin XM and Dong Z. Essentials of Apoptosis: A guide for basic and clinical research, Humana Press, Totowa, New Jersey, 2003; 177-200