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Science Forum Index » Life Extension Forum » Selenomethionine may induce redox sensitive p53 DNA repair
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| Tim |
Posted: Fri Jan 02, 2004 1:30 pm |
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Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14548-53. Epub 2002 Sep
30. Related Articles, Links
Comment in:
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):13969-71.
Selenomethionine regulation of p53 by a ref1-dependent redox
mechanism.
Seo YR, Kelley MR, Smith ML.
Department of Microbiology, Walther Oncology Center, and Walther
Cancer Institute, Indiana University School of Medicine, Indianapolis,
IN 46208, USA.
The cancer chemopreventive properties of selenium compounds are well
documented, yet little is known of the mechanism(s) by which these
agents inhibit carcinogenesis. We show that selenium in the form of
selenomethionine (SeMet) can activate the p53 tumor suppressor protein
by a redox mechanism that requires the redox factor Ref1. Assays to
measure direct reduction/oxidation of p53 showed a SeMet-dependent
response that was blocked by a dominant-negative Ref1. By using a
peptide containing only p53 cysteine residues 275 and 277, we
demonstrate the importance of these residues in the SeMet-induced
response. SeMet induced sequence-specific DNA binding and
transactivation by p53. Finally, cellular responses to SeMet were
determined in mouse embryo fibroblasts wild-type or null for p53
genes. The evidence suggests that the DNA repair branch of the p53
pathway was activated. The central relevance of DNA repair to cancer
prevention is discussed.
PMID: 12357032 [PubMed - indexed for MEDLINE]
FULL TEXT
http://www.pnas.org/cgi/content/full/99/22/14548
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