STRUCTURE ANS FUNCTION OF THE MEN1 GENE AND ITS PROTEIN PRODUCT, MENIN

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The MEN1 gene is a tumor suppressor gene identified by positional cloning by an NIH collaborative group including members of MDB. Germline mutations in the gene are found in affected subjects of MEN1 kindreds, and somatic mutations in the gene have been identified in sporadic endocrine and other tumors. The gene encodes a 610 residue protein termed menin without homology to other known proteins and without obvious functional motifs. We have initiated a series of studies aimed at defining the structure, function, subcellular localization, and range of expression of menin. We have generated a series of polyclonal peptide antisera that have proved useful in immunoblot and immunoprecipitation studies. Furthermore,these antibodies detect the expression of recombinant forms of menin to be used for structural and biochemical analyses.The cDNA encoding menin has been transiently transfected in 293 cells and antibodies used to monitor its expression after subcellular fractionation. These studies will be extended to mutant forms of the protein. Efforts are also being directed at identifying biochemical activities associated with menin, and defining changes in mRNA and/or protein expression in cells and tissues under a variety of conditions, e.g. states of endocrine hyperplasia.