Negative regulation of TLR inflammatory signaling by the SUMO-deconjugating enzyme SENP6.

ABSTRACT: 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-κB-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-κB essential modifier (NEMO/IKKγ), and this impairs the deubiquitinase CYLD to bind NEMO, thu

SUBMITTER: Liu X 

PROVIDER: S-EPMC3694847 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature