Oncogenic phosphatase amplification

Post-translational regulation of p53 regulates its activity and tumor suppressor functions. In an Advanced Online Publication in Nature Genetics, Dmitry Bulavin and colleagues from the National Institutes of Health describe how oncogenic Ras regulates p53 phosphorylation (Nat Genet 2002, DOI:10.1038/ng894).

Bulavin et al. used antibodies specific for different modified forms of p53 and showed that oncogenic Ras induced p53, accumulation and phosphorylation of two specific serine residues that are substrates of p38 MAP kinase. They found that the p53-inducible phosphatase PPM1D abrogates p53 phosphorylation indirectly by inhibiting MAP kinase activity; overexpression of PPM1D was oncogenic in p53-expressing cells. They found evidence for amplification and overexpression of the human PPM1D gene in breast cancer cells expressing wild-type p53.

An accompanying report by Jing Li and colleagues provides additional evidence for PPM1D locus amplification and overexpression in breast cancer cells (Nat Genet 2002, DOI:10.1038/ng888).

These results suggest...