The menin gene

Multiple endocrine neoplasia type I (MEN-1) is an autosomal dominant syndrome featuring tumors of endocrine origin. Heterozygous germline mutations in the MEN-1 tumor suppressor gene predispose MEN-1 patients to tumor development, mainly in parathyroid, pancreatic islet cells, and the anterior pituitary gland. Since the MEN-1-encoded protein, menin, is ubiquitously expressed, the endocrine-specific nature in MEN-1 patients remains unexplained. This chapter provides an overview of the MEN-1 gene, including patterns of mutations identified since its discovery in 1997. Different menin-interacting protein partners and menin's proposed molecular functions are also discussed. Lastly, various animal models of MEN-1 are described in detail. While analyses utilizing genetic, biochemical, and physiological techniques have led to a better understanding of menin's mechanisms of action, much is yet to be elucidated about menin's role in MEN-1 tumorigenesis.