Menin, the product of the MEN1 gene, is a nuclear protein

Siradanahalli C. Guru, Paul K. Goldsmith, A. Lee Burns, Stephen J. Marx, Allen M. Spiegel, Francis S. Collins, Settara C. Chandrasekharappa

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Abstract

The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.

Original languageEnglish (US)
Pages (from-to)1630-1634
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998
Externally publishedYes

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    Guru, S. C., Goldsmith, P. K., Lee Burns, A., Marx, S. J., Spiegel, A. M., Collins, F. S., & Chandrasekharappa, S. C. (1998). Menin, the product of the MEN1 gene, is a nuclear protein. Proceedings of the National Academy of Sciences of the United States of America, 95(4), 1630-1634. https://doi.org/10.1073/pnas.95.4.1630