| First Author | Liu X | Year | 2013 |
| Journal | PLoS Pathog | Volume | 9 |
| Issue | 6 | Pages | e1003480 |
| PubMed ID | 23825957 | Mgi Jnum | J:213375 |
| Mgi Id | MGI:5584246 | Doi | 10.1371/journal.ppat.1003480 |
| Citation | Liu X, et al. (2013) Negative regulation of TLR inflammatory signaling by the SUMO-deconjugating enzyme SENP6. PLoS Pathog 9(6):e1003480 |
| abstractText | The signaling of Toll-like receptors (TLRs) induces host defense against microbial invasion. Protein posttranslational modifications dynamically shape the strength and duration of the signaling pathways. It is intriguing to explore whether de-SUMOylation could modulate the TLR signaling. Here we identified SUMO-specific protease 6 (SENP6) as an intrinsic attenuator of the TLR-triggered inflammation. Depletion of SENP6 significantly potentiated the NF-kappaB-mediated induction of the proinflammatory genes. Consistently, SENP6-knockdown mice were more susceptible to endotoxin-induced sepsis. Mechanistically, the small ubiquitin-like modifier 2/3 (SUMO-2/3) is conjugated onto the Lysine residue 277 of NF-kappaB essential modifier (NEMO/IKKgamma), and this impairs the deubiquitinase CYLD to bind NEMO, thus strengthening the inhibitor of kappaB kinase (IKK) activation. SENP6 reverses this process by catalyzing the de-SUMOylation of NEMO. Our study highlights the essential function of the SENP family in dampening TLR signaling and inflammation. |
