1998/02/17 by Siradanahalli C. Guru, Paul K. Goldsmith, A. Lee Burns +4 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Neuroendocrine Tumor Research Advances #Neuroblastoma Research and Treatments #Microtubule and mitosis dynamics #MEN1 #Frameshift mutation #Nuclear localization sequence #Biology #Subcellular localization #Gene #Gene product #Nuclear protein #Molecular biology #Missense mutation #Protein subcellular localization prediction #Mutation #Genetics #Multiple endocrine neoplasia #Gene expression #Transcription factor
paper · doi:10.1073/pnas.95.4.1630
openalex publication_date 1998/02/17 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/22
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.