title: The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5 activity in a substrate-specific manner.
abstract: We previously identified DAL-1/4.1B as a growth suppression protein involved in the pathogenesis of lung, breast, and meningioma tumors. Using yeast two-hybrid interaction cloning, protein arginine N-methyltransferase 3 (PRMT3) was originally identified as a DAL-1/4.1B-interacting protein. PRMTs catalyze the sequential transfer of methyl groups from S-adeonsyl-l-methionine to the guanidino nitrogens of arginine residues in proteins, the effect of which can include regulation of signal transduction, transcription regulation, and RNA transport, suggesting that modulating this event may have far-reaching impact. In this study, we assessed the impact of DAL-1/4.1B binding on the activity of another family member, PRMT5, both in vitro and in cells. In contrast to PRMT3, DAL-1/4.1B was found to mediate PRMT5 by either inhibiting (Sm proteins) or enhancing (myelin basic protein) protein methylation. We propose that this interaction between a tumor suppressor and a post-translational methylation enzyme is of biological importance in controlling tumorigenesis.
authors.affiliation: David and Doreen Hermelin Laboratory of Molecular Oncogenetics, Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Martha E
authors.initials: ME
authors.lastname: Roemer
authors.forename: Irene F
authors.initials: IF
authors.lastname: Newsham
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008840:Microfilament Proteins; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases