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 journalArticle

6 Citations (Scopus)

Abstract

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
Volume36
Issue number24
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Caspases
Ubiquitin
Cell Survival
Cell Death
Caspase 6
Effector Caspases
Apoptosis
Ubiquitination
Aspartic Acid
Caspase 3
Neoplasms
Homeostasis
Tumor Necrosis Factor-alpha
Mutation
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Regulation of linear ubiquitin chain assembly complex by caspase-mediated cleavage of RNF31. / Joo, Donghyun; Tang, Yong; Blonska, Marzenna; Jin, Jianping; Zhao, Xueqiang; Lin, Xin.

In: Molecular and Cellular Biology, Vol. 36, No. 24, 2016, p. 3010-3018.

Research output: Contribution to journalArticle

Joo, Donghyun ; Tang, Yong ; Blonska, Marzenna ; Jin, Jianping ; Zhao, Xueqiang ; Lin, Xin. / Regulation of linear ubiquitin chain assembly complex by caspase-mediated cleavage of RNF31. In: Molecular and Cellular Biology. 2016 ; Vol. 36, No. 24. pp. 3010-3018.
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