Methylation of the phosphatase‐transcription activator EYA1 by protein arginine methyltransferase 1: mechanistic, functional, and structural studies. Issue 6 (17th February 2017)

• Record Type: Journal Article
• Authors: Li, Xingguo; Eberhardt, Allison; Hansen, Jeanne N.; Bohmann, Dirk; Li, Haitao; Schor, Nina F.
• Is Part Of: FASEB journal. Volume 31:Issue 6(2017)
• Page Start: 2327
• Page End: 2339
• Publication Date: 2017-02-17
• Subjects: protein phosphatase -- post‐translational modification -- protein arginine methylation -- γ‐H2A.X -- Drosophila -- eye development; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201601050RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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 its in vitro phosphatase activity and in vivo function during Drosophila eye development. EYA1 physically interacts with protein arginine methyltransferase 1, which methylates EYA1 at these residues both in vitro and 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. FASEB J. 31, 2327–2339 (2017). www.fasebj.org