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Mol Cell. 2013 Oct 10;52(1):37-51. doi: 10.1016/j.molcel.2013.08.039. Epub 2013 Sep 26.

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

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Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford OX3 7DQ, UK; Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, A(∗)STAR (Agency for Science, Technology, and Research), Biopolis, Singapore 138672, Singapore.


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.

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