Continuing last week’s post about protein methylation in cellular inflammatory responses, we would like to call attention to the recent publication by Zhang et al. The authors explain how PRMT1-SMAD6 signaling may represent a new target for reducing the immune response in periodontitis (see Figure):
Lipopolysacchride (LPS) from oral pathogens activate toll-like receptors (TLR) which recruit MyD88, an adaptor protein, which activates protein complexes of IRAK, TRAF6, and TAK1. These activated complexes switch on the nuclear translocation of NFκB to activate pro-inflammatory cytokines, chemokines, and metalloproteases. The end result is periodontitis.
The key findings of Zhang et al. provide a molecular explanation of how the anti-inflammatory transforming growth β (TFGβ) family of cytokines can act to counter-balance TLR signalling. When SMAD6 is methylated by PRMT1 on arginine 81, it binds to MyD88. This protein-protein interaction recruits E3 Ligase and Smurf1 to promote MyD88 degradation via the ubiquitin-proteasome pathway. The reduction in cellular MyD88, thus mitigates the downstream events that lead to periodontitis.
As we study the effects of protein arginine methylation on cellular inflammation we plan to share more publications that pique our interest. Thanks for reading!
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