title: Methylation of the phosphatase-transcription activator EYA1 by protein arginine methyltransferase 1: mechanistic, functional, and structural studies.
abstract: The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for itsin vitrophosphatase activity andin vivofunction duringDrosophilaeye development. EYA1 physically interacts with protein arginine methyltransferase 1, which methylates EYA1 at these residues bothin vitroand in cultured mammalian and insect cells. Moreover, we show that wild-type, but not methylation-defective, EYA1 associates with γ-H2A.X in response to ionizing radiation. Taken together, our results identify the conserved arginine residues of EYA1 that play an important role for its activity, thus implicating arginine methylation as a novel regulatory mechanism of EYA function.-Li, X., Eberhardt, A., Hansen, J. N., Bohmann, D., Li, H., Schor, N. F. Methylation of the phosphatase-transcription activator EYA1 by protein arginine methyltransferase 1: mechanistic, functional, and structural studies.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA; xingguo_li@urmc.rochester.edu.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Eberhardt
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Jeanne N
authors.initials: JN
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bohmann
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, and.|School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA; nina_schor@urmc.rochester.edu.
authors.forename: Nina F
authors.initials: NF
authors.lastname: Schor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011484:Protein-Arginine N-Methyltransferases; D010744:Phosphoric Monoester Hydrolases; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Drosophila eye development; post-translational modification; protein arginine methylation; protein phosphatase; γ-H2A.X