PRMT5-mediated regulatory arginine methylation of RIPK3
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 3.16 MB, PDF document
The TNF receptor-interacting protein kinases (RIPK)-1 and 3 are regulators of extrinsic cell death response pathways, where RIPK1 makes the cell survival or death decisions by associating with distinct complexes mediating survival signaling, caspase activation or RIPK3-dependent necroptotic cell death in a context-dependent manner. Using a mass spectrometry-based screen to find new components of the ripoptosome/necrosome, we discovered the protein-arginine methyltransferase (PRMT)-5 as a direct interaction partner of RIPK1. Interestingly, RIPK3 but not RIPK1 was then found to be a target of PRMT5-mediated symmetric arginine dimethylation. A conserved arginine residue in RIPK3 (R486 in human, R415 in mouse) was identified as the evolutionarily conserved target for PRMT5-mediated symmetric dimethylation and the mutations R486A and R486K in human RIPK3 almost completely abrogated its methylation. Rescue experiments using these non-methylatable mutants of RIPK3 demonstrated PRMT5-mediated RIPK3 methylation to act as an efficient mechanism of RIPK3-mediated feedback control on RIPK1 activity and function. Therefore, this study reveals PRMT5-mediated RIPK3 methylation as a novel modulator of RIPK1-dependent signaling.
Original language | English |
---|---|
Article number | 14 |
Journal | Cell Death Discovery |
Volume | 9 |
Number of pages | 9 |
ISSN | 2058-7716 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
© 2023. The Author(s).
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 333470327