RNF167-mediated ubiquitination of Tollip inhibits TNF-?-triggered NF-?B and MAPK activation.

Toll-interacting protein (Tollip) is a multifunctional regulator in cellular activities. However, whether its functions are subjected to post-translational modifications remains elusive. Here, we identified ubiquitination as a post-translational modification on Tollip. We found that Tollip interacted with ring finger protein 167 (RNF167) through its C-terminal coupling of ubiquitin to ER ...
degradation (CUE) domain, and RNF167 functioned as the potential E3 ligase to attach K33-linked poly-ubiquitin chains to the Lys235 (K235) site of Tollip. Furthermore, we discovered Tollip could inhibit TNF-?-induced nuclear factor-kappa B (NF-?B) and mitogen-activated protein kinase (MAPK) activation, and substitution of Lys235 on Tollip to arginine failed to suppress TNF-?-NF-?B/MAPK (JNK) cascades, revealing the role of Tollip and its ubiquitination in NF-?B/MAPK pathways. Thus, our study reveals the novel biological function of Tollip and RNF167-dependent ubiquitination of Tollip in TNF-? signaling.
Mesh Terms:
Mitogen-Activated Protein Kinases, NF-kappa B, Tumor Necrosis Factor-alpha, Ubiquitin, Ubiquitination
FASEB J
Date: Aug. 01, 2023
Download Curated Data For This Publication
253984
Switch View:
  • Interactions 7