The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation.
Oncogene
; 20(36): 4917-25, 2001 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-11526476
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genes Supressores de Tumor
/
NF-kappa B
/
Proteínas Proto-Oncogênicas
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos