The Mammalian Immediate-early TIS21 Protein and the Leukemia-associated BTG1 Protein Interact with a Protein-arginine N-Methyltransferase

• Published in: The Journal of biological chemistry 1996-06, Vol.271 (25), p.15034-15044
• Main Authors: Lin, W J, Gary, J D, Yang, M C, Clarke, S, Herschman, H R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA Primers; DNA, Complementary; Escherichia coli; Genes, Tumor Suppressor; Glutathione Transferase - biosynthesis; Humans; Immediate-Early Proteins - metabolism; Intracellular Signaling Peptides and Proteins; Leukemia, Lymphocytic, Chronic, B-Cell; Macromolecular Substances; Mammals; Methyltransferases - metabolism; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - chemistry; Neoplasm Proteins - metabolism; Open Reading Frames; Polymerase Chain Reaction; Protein Biosynthesis; Protein Structure, Secondary; Protein-Arginine N-Methyltransferases; Proteins - chemistry; Proteins - metabolism; Rats; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Sequence Homology, Amino Acid; Tumor Suppressor Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.25.15034

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 N G -monomethyl and N G , N G -dimethylarginine (asymmetric). We term the protein- arginine N -methyltransferase (EC) gene “PRMT1,” for rotein-a ginine ethyl ransferase 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.