Arginine Methylation-Dependent Reader-Writer Interplay Governs Growth Control by E2F-1

作者：Zheng Shunsheng; Moehlenbrink Jutta; Lu Yi Chien; Zalmas Lykourgos Panagiotis; Sagum Carl A; Carr Simon; McGouran Joanna F; Alexander Leila; Fedorov Oleg; Munro Shonagh; Kessler Benedikt; Bedford Mark T; Yu Qiang; La Thangue Nicholas B^*

来源：Molecular Cell, 2013, 52(1): 37-51.

DOI：10.1016/j.molcel.2013.08.039

The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase 1 (PRMT1) and symmetric dimethylating PRMT5 and relate the marks to different functional consequences of E2F-1 activity. Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favors proliferation by antagonizing methylation by PRMT1. The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell-cycle progression mode. The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN downregulates E2F-1 apoptotic activity. Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity.

• 出版日期2013-10-10