Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1

Journal article

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. © 2013 Elsevier Inc.

Authors: Zheng, S; Moehlenbrink, J; Lu, Y; Zalmas, L; Carr, S

• Journal: Molecular Cell
• Volume: 52
• Issue: 1
• Pages: 37-51
• Publication date: 2013-10-10
• DOI: 10.1016/j.molcel.2013.08.039
• EISSN: 1097-4164
• ISSN: 1097-2765