title: Phosphorylation of the menin tumor suppressor protein on serine 543 and serine 583.
abstract: Multiple endocrine neoplasia type 1 (MEN-1) is a heritable syndrome typified by tumors in multiple endocrine organs, including the pituitary, parathyroids, and pancreatic islets. MEN-1 is attributable to mutations in the MEN1 tumor-suppressor gene that encodes the menin protein. Recent studies have implicated menin in transcriptional regulation and in covalent histone modification; however, little is known about modifications of the menin protein. Here, we report that menin is subject to phosphorylation on serine residues, including Ser543 and Ser583. Phosphorylation-defective mutants of either or both of these residues retain the associated histone methyltransferase activity of menin, as well as binding to the trithorax complex members Ash2L, Rbbp5, and MLL2 and to RNA polymerase II. Chromatin immunoprecipitation experiments reveal that binding of menin to the Hoxc8 locus is not affected by phosphorylation on Ser543 or Ser583.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hughes
authors.forename: Orit
authors.initials: O
authors.lastname: Rozenblatt-Rosen
authors.forename: Suraj
authors.initials: S
authors.lastname: Nannepaga
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018922:HL-60 Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D011496:Protein Methyltransferases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012694:Serine; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C120898:KMT2D protein, human; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D012694:Serine; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase