The tumor suppressor protein menin interacts with NF-κb proteins and inhibits NF-κb-mediated transactivation

Christina Heppner, Karl Y. Bilimoria, Sunita K. Agarwal, MaryBeth Kester, Leslie J. Whitty, Siradanahalli C. Guru, Settara C. Chandrasekharappa, Francis S. Collins, Allen M. Spiegel, Stephen J. Marx, A. Lee Burns

Research output: Contribution to journalArticle

200 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4917-4925
Number of pages9
JournalOncogene
Volume20
Issue number36
DOIs
StatePublished - Aug 16 2001

Keywords

  • Men1
  • Men1 gene
  • Menin
  • Nf-κb
  • Oncogene
  • Rel-homology domain
  • Transcriptional repression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Heppner, C., Bilimoria, K. Y., Agarwal, S. K., Kester, M., Whitty, L. J., Guru, S. C., Chandrasekharappa, S. C., Collins, F. S., Spiegel, A. M., Marx, S. J., & Burns, A. L. (2001). The tumor suppressor protein menin interacts with NF-κb proteins and inhibits NF-κb-mediated transactivation. Oncogene, 20(36), 4917-4925. https://doi.org/10.1038/sj.onc.1204529