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 its phosphatase activity and function during eye development. EYA1 physically interacts with protein arginine methyltransferase 1, which methylates EYA1 at these residues both 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.

The Eya phosphatase: Its unique role in cancer

“…All other known HAD protein phosphatases dephosphorylate Ser/Thr residues, while Eya targets phosphorylated Tyr 46 . Schor and colleagues recently demonstrated that methylation of the highly conserved residues R304 and R306 in Eya1 is essential for its Tyr phosphatase activity, revealing a possible mechanism through which the Tyr phosphatase activity of Eya can be regulated 47 .…”