期刊
ONCOGENE
卷 20, 期 36, 页码 4917-4925出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204529
关键词
MEN1; MEN1 gene; menin; NF-kappa B; transcriptional repression; oncogene; Rel-homology domain
Multiple endocrine neoplasia type I is an autosomal dominant tumor syndrome. Manifestations include neoplasms of the parathyroid glands, entero pancreatic 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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