Interaction between NPM1 which is deeply related with the prognosisof leukemia and the ETS family of transcription factor, MEF

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Myeloid ELF1-like factor (MEF), a member of the ETS transcription factors, can function as an oncogene. We found that MEF directly forms a complex with NPM1. Functional analyses showed that wild-type NPM1 inhibited the DNA-binding and transcriptional activity of MEF on the HDM2 promoter whereas NPM1 mutant protein (Mt-NPM1) enhanced these activities of MEF. It also related to the transformation of NIH3T3 cells by MEF. In addition, clinical leukemia samples with NPM1 mutations had higher HDM2 mRNA expression. Our data suggest that enhanced HDM2 expression induced by mutant NPM1 may have a role in MEF/ELF4-dependent leukemogenesis. (J Biol Chem 2013;288(13):9457-67.)