Menin: The Protein Behind the MEN1 Syndrome

The cloning of the MEN1 gene in 1997 led to the characterization of menin, the protein behind the multiple endocrine neoplasia Type 1 syndrome. Menin, a novel nuclear protein with no homologyto other gene products, is expressed ubiquitously. MEN1 missense mutations are dispersed along the coding region of the gene but are more common in the most conserved regions. Likewise, domains of protein interaction often correspond to the more conserved segments of menin. These protein interactions are generally facilitated by multiple domains or encompass a large portion of menin. The exception to this rule is a small stretch of amino acids mediating the interaction of menin with the mSin3A corepressor and histone deacetylase complexes. The C-terminal region of menin harbors several nuclear localization signals that play redundant functions in the localization of menin to the nuclear compartment. The nuclear localization signals are also important for the interaction of menin with the nuclear matrix. Menin is the target of several kinases and a candidate substrate of the ATM/ATR kinases, implying a role for this tumor suppressor in the DNA damage response. Menin is highly conserved from Drosophila to human but is absent in the nematode and in yeast.