The tumor suppressor protein menin interacts with NF-[kappa]B proteins and inhibits NF-[kappa]B-mediated transactivation

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 seq...

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Veröffentlicht in:Oncogene 2001-08, Vol.20 (36), p.4917
Hauptverfasser: 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, A Lee Burns
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container_end_page
container_issue 36
container_start_page 4917
container_title Oncogene
container_volume 20
creator 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
A Lee Burns
description 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.
doi_str_mv 10.1038/sj.onc.1204529
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subjects Amino acids
Antibodies
Molecular weight
Mutation
Proteins
Transcription factors
Tumors
title The tumor suppressor protein menin interacts with NF-[kappa]B proteins and inhibits NF-[kappa]B-mediated transactivation
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