We have shown that inherited mutations in the MEN1 gene predispose individuals to develop multiple endocrine neoplasia type 1 (MEN1), characterized by multiple tumors of the parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tissues. We have shown that the MEN1 encoded protein (menin) is located primarily in the nucleus, and it interacts with JunD, a member of the AP1 family transcription factors. The menin-JunD interaction results in the repression of JunD- induced transcription, and the protein domains involved in their interaction have been identified. Also, potential interactions of menin with other cellular proteins are being investigated by the yeast two- hybrid system, co-immunoprecipitation and GST?menin pull-down assays. MEN1 homologous genes from mouse, zebrafish and Drosophila have been identified. In order to understand the functional role of menin, a mouse knockout model is being generated by homologous recombination, using the cre-lox system to allow tissue specific inactivation. - Cancer Research