title: The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase.
abstract: The TIS21 immediate-early gene and leukemia-associated BTG1 gene encode proteins with similar sequences. Two-hybrid analysis identified a protein that interacts with TIS21 and BTG1. Sequence motifs associated with S-adenosyl-L-methionine binding suggested this protein might have methyltransferase activity. A glutathione S-transferase (GST) fusion of the putative methyltransferase modifies arginine residues, in appropriate protein substrates, to form NG-monomethyl and NG,NG-dimethylarginine (asymmetric). We term the protein- arginine N-methyltransferase (EC 2.1.1.23) gene "PRMT1, " for protein-arginine methyltransferase 1. GST-TIS21 and GST-BTG1 fusion proteins qualitatively and quantitatively modulate endogenous PRMT1 activity, using control and hypomethylated RAT1 cell extracts as methyl-accepting substrates. PRMT1 message appears ubiquitous, and is constitutive in mitogen-stimulated cells. Modulation of PRMT1 activity by transiently expressed regulatory subunits may be an additional mode of signal transduction following ligand stimulation.
authors.affiliation: Molecular Biology Institute, Department of Chemistry and Biochemistry University of California, Los Angeles, 90095, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Lin
authors.forename: J D
authors.initials: JD
authors.lastname: Gary
authors.forename: M C
authors.initials: MC
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Clarke
authors.forename: H R
authors.initials: HR
authors.lastname: Herschman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D004926:Escherichia coli; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D046911:Macromolecular Substances; D008322:Mammals; D008780:Methyltransferases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D011484:Protein-Arginine N-Methyltransferases; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
chemical_list: C489553:Btg1 protein, rat; D017931:DNA Primers; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human; C074086:BTG1 protein, human; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases; D005982:Glutathione Transferase