title: The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation.
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-kappaB proteins p50, p52 and p65 were found to interact specifically and directly with menin in vitro and in vivo. The region of NF-kappaB 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-kappaB sites in a dose-dependent and specific manner. Also, PMA (phorbol 12-myristate 13-acetate)-stimulated NF-kappaB activation is suppressed by menin. These observations suggest that menin's ability to interact with NF-kappaB proteins and its modulation of NF-kappaB transactivation contribute to menin's tumor suppressor function.
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: C
authors.initials: C
authors.lastname: Heppner
authors.forename: K Y
authors.initials: KY
authors.lastname: Bilimoria
authors.forename: S K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: M
authors.initials: M
authors.lastname: Kester
authors.forename: L J
authors.initials: LJ
authors.lastname: Whitty
authors.forename: S C
authors.initials: SC
authors.lastname: Guru
authors.forename: S C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: F S
authors.initials: FS
authors.lastname: Collins
authors.forename: A M
authors.initials: AM
authors.lastname: Spiegel
authors.forename: S J
authors.initials: SJ
authors.lastname: Marx
authors.forename: A L
authors.initials: AL
authors.lastname: Burns
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: C105373:MEN1 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D005982:Glutathione Transferase; D013755:Tetradecanoylphorbol Acetate