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Department of Biology, University of York, Heslington, York YO1 5DD, United Kingdom
In human tumors, many different point mutations of the p53 gene knock out suppressor function and induce the p53 polypeptide to adopt an immunologically distinct, "mutant" conformation. Here we show that exposure to the metal chelator 1,10-phenanthroline induces wild-type p53 to adopt the mutant conformation and that this process is reversible. Conversion to mutant phenotype also occurs after exposure to (a) an organic mercurial reagent targeting cysteinyl residues and (b) low concentrations of mercury or cadmium. We propose that binding of metal ions, most probably zinc, to conserved cysteinyl residues stabilizes the tertiary structure of wild-type p53.
1 This work was supported by a Yorkshire Cancer Research Campaign program grant to J. M.
2 To whom requests for reprints should be addressed.
Received 1/28/93. Accepted 3/ 5/93.
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