Molecular cell, 2013-10, Vol.52 (1), p.37-51
2013
Details
- Autor(en) / Beteiligte
- Titel
- Arginine Methylation-Dependent Reader-Writer Interplay Governs Growth Control by E2F-1
- Ist Teil von
- Molecular cell, 2013-10, Vol.52 (1), p.37-51
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •PRMT1 and PRMT5 competitively methylate E2F-1•Arginine methylation directs E2F-1 along different biological pathways•DNA damage augments, whereas cyclin A binding hinders, PRMT1 methylation•Tudor domain protein p100-TSN recognizes the symmetric methylation mark
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2013.08.039Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4129656
- Format
- –
- Schlagworte
- Amino Acid Motifs, Apoptosis, Arginine, cell cycle, Cell Line, Tumor, Cell Proliferation, Chromatin Assembly and Disassembly, Cyclin A - metabolism, cyclins, DNA, DNA Damage, E2F1 Transcription Factor - genetics, E2F1 Transcription Factor - metabolism, Gene Expression Regulation, Humans, Methylation, methyltransferases, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Protein-Arginine N-Methyltransferases - genetics, Protein-Arginine N-Methyltransferases - metabolism, Repressor Proteins - genetics, Repressor Proteins - metabolism, RNA Interference, Signal Transduction, Transcription, Genetic, Transfection