| First Author | Zhang X | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 1 | Pages | 224-235 |
| PubMed ID | 28683316 | Mgi Jnum | J:254286 |
| Mgi Id | MGI:6104212 | Doi | 10.1016/j.celrep.2017.05.070 |
| Citation | Zhang X, et al. (2017) Positive Regulation of Interleukin-1beta Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation. Cell Rep 20(1):224-235 |
| abstractText | Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1beta positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1beta from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1beta glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases. |
