Abstract
Multiple endocrine neoplasia type 1 is an autosomal dominant tumor syndrome. Manifestations include neoplasms of the parathyroid glands, enteropancreatic neuroendocrine cells, and the anterior pituitary gland. The MEN1 tumor suppressor gene encodes menin, a 610 amino acid nuclear protein without sequence homology to other proteins. To elucidate menin function, we used immunoprecipitation to identify interacting proteins. The NF-κB proteins p50, p52 and p65 were found to interact specifically and directly with menin in vitro and in vivo. The region of NF-κB proteins sufficient for binding to menin is the N-terminus. Furthermore, amino acids 305–381 of menin are essential for this binding. Menin represses p65-mediated transcriptional activation on NF-κB sites in a dose-dependent and specific manner. Also, PMA (phorbol 12-myristate 13-acetate)-stimulated NF-κB activation is suppressed by menin. These observations suggest that menin's ability to interact with NF-κB proteins and its modulation of NF-κB transactivation contribute to menin's tumor suppressor function.
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Acknowledgements
We thank Dr Paul K Goldsmith (NIDDK) for purified menin antibodies, Dr George Poy (NIDDK) for DNA sequencing and Dr Regina M Collins (NIDDK) for cell culture assistance. Furthermore, we thank Dr Ulrich Siebenlist (NIAID) for helpful discussion and providing the GST-50 construct and Dr Nancy R Rice (NCl) for the p100 construct.
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Heppner, C., Bilimoria, K., Agarwal, S. et al. The tumor suppressor protein menin interacts with NF-κB proteins and inhibits NF-κB-mediated transactivation. Oncogene 20, 4917–4925 (2001). https://doi.org/10.1038/sj.onc.1204529
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DOI: https://doi.org/10.1038/sj.onc.1204529
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