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- Title
The tumor suppressor protein menin interacts with NF-κB proteins and inhibits NF-κB-mediated transactivation.
- Authors
Heppner, Christina; Bilimoria, Karl Y; Agarwal, Sunita K; Kester, MaryBeth; Whitty, Leslie J; Guru, Siradanahalli C; Chandrasekharappa, Settara C; Collins, Francis S; Spiegel, Allen M; Marx, Stephen J; Burns, A Lee
- 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. Oncogene (2001) 20, 4917–4925.
- Subjects
TUMORS; SYNDROMES; PARATHYROID glands; PROTEINS; AMINO acids
- Publication
Oncogene, 2001, Vol 20, Issue 36, p4917
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204529