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

Project: Research project

Project Details

Description

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
in conjunction with studies of GFP-tagged menin conducted by our
collaborators in NHGRI have shown that menin is primarily
localized to the nucleus. A drosophila cell expression system has
been established with menin stably transfected. This has enabled us
to purify menin from cultured cells using immunoaffinity
chromatography. Purified menin will be used for detailed
biochemical and structural studies aimed at elucidating the normal
function of this tumor suppressor gene product, and clarifying how
mutations in the gene cause loss of function.
StatusNot started

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Immunology

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