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The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-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 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.

Pubmed ID: 11526476

Authors

  • Heppner C
  • Bilimoria KY
  • Agarwal SK
  • Kester M
  • Whitty LJ
  • Guru SC
  • Chandrasekharappa SC
  • Collins FS
  • Spiegel AM
  • Marx SJ
  • Burns AL

Journal

Oncogene

Publication Data

August 16, 2001

Associated Grants

None

Mesh Terms

  • Animals
  • COS Cells
  • Cell Line
  • Genes, Tumor Suppressor
  • Glutathione Transferase
  • HeLa Cells
  • Humans
  • NF-kappa B
  • Neoplasm Proteins
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Tetradecanoylphorbol Acetate
  • Transcriptional Activation