Differential binding of the Menin tumor suppressor protein to JunD isoforms.

The role of the Jun family of proteins (c-Jun, JunB, and JunD) in oncogenesis has been extensively studied, but the distinct biological roles of each Jun protein is not known. For example, whereas c-Jun can transform primary cells in cooperation with an activated ras oncogene, JunD antagonizes ras-mediated transformation. We have discovered that two isoforms of the JunD transcription factor are ubiquitously expressed, resulting from use of an alternative translation start codon within the JunD mRNA. Here we report the first characterized functional difference between these JunD isoforms; only the full-length isoform of JunD binds to the Menin tumor suppressor protein. Furthermore, Menin suppresses transcriptional activity of the full-length but not the truncated isoform of JunD, which identifies the full-length JunD isoform as a functional target of Menin.