Regulation of Linear Ubiquitin Chain Assembly Complex by Caspase-Mediated Cleavage of RNF31.

Cell death and survival signaling pathways have opposed but fundamental functions for various cellular processes and maintain cell homeostasis through cross talk. Here we report a novel mechanism of interaction between these two pathways through the cleavage of RNF31 by caspases. RNF31, a component of the linear ubiquitin chain assembly ...
complex (LUBAC), regulates cell survival by inducing linear ubiquitination of NF-κB signaling components. We found that RNF31 is cleaved under apoptosis conditions through various stimulations. The effector caspases caspase 3 and caspase 6 are responsible for this event, and aspartates 348, 387, and 390 were identified as target sites for this cleavage. Cleavage of RNF31 suppressed its ability to activate NF-κB signaling; thus, mutation of cleavage sites inhibited the induction of apoptosis by treatment with tumor necrosis factor alpha (TNF-α). Our findings elucidate a novel regulatory loop between cell death and the survival signal and may provide guidance for the development of therapeutic strategies for cancers through the sensitization of tumor cells to death-inducing drugs.
Mesh Terms:
A549 Cells, Apoptosis, Aspartic Acid, Binding Sites, Caspase 3, Caspase 6, Cell Line, Cell Survival, Gene Expression Regulation, HCT116 Cells, HEK293 Cells, HT29 Cells, HeLa Cells, Humans, Mutation, NF-kappa B, Proteolysis, Signal Transduction, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitination
Mol. Cell. Biol.
Date: Dec. 15, 2016
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