Regulation of linear ubiquitin chain assembly complex by caspase-mediated cleavage of RNF31

Donghyun Joo, Yong Tang, Marzenna Blonska, Jianping Jin, Xueqiang Zhao, Xin Lin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3010-3018
Number of pages9
JournalMolecular and cellular biology
Issue number24
StatePublished - 2016
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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