論文

国際誌
2021年12月

MIND bomb 2 prevents RIPK1 kinase activity-dependent and -independent apoptosis through ubiquitylation of cFLIPL

Communications Biology
  • Osamu Nakabayashi
  • ,
  • Hirotaka Takahashi
  • ,
  • Kenta Moriwaki
  • ,
  • Sachiko Komazawa-Sakon
  • ,
  • Fumiaki Ohtake
  • ,
  • Shin Murai
  • ,
  • Yuichi Tsuchiya
  • ,
  • Yuki Koyahara
  • ,
  • Yasushi Saeki
  • ,
  • Yukiko Yoshida
  • ,
  • Soh Yamazaki
  • ,
  • Fuminori Tokunaga
  • ,
  • Tatsuya Sawasaki
  • ,
  • Hiroyasu Nakano

4
1
開始ページ
80
終了ページ
80
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s42003-020-01603-y
出版者・発行元
Springer Science and Business Media {LLC}

Mind bomb 2 (MIB2) is an E3 ligase involved in Notch signalling and attenuates TNF-induced apoptosis through ubiquitylation of receptor-interacting protein kinase 1 (RIPK1) and cylindromatosis. Here we show that MIB2 bound and conjugated K48- and K63-linked polyubiquitin chains to a long-form of cellular FLICE-inhibitory protein (cFLIPL), a catalytically inactive homologue of caspase 8. Deletion of MIB2 did not impair the TNF-induced complex I formation that mediates NF-κB activation but significantly enhanced formation of cytosolic death-inducing signalling complex II. TNF-induced RIPK1 Ser166 phosphorylation, a hallmark of RIPK1 death-inducing activity, was enhanced in MIB2 knockout cells, as was RIPK1 kinase activity-dependent and -independent apoptosis. Moreover, RIPK1 kinase activity-independent apoptosis was induced in cells expressing cFLIPL mutants lacking MIB2-dependent ubiquitylation. Together, these results suggest that MIB2 suppresses both RIPK1 kinase activity-dependent and -independent apoptosis, through suppression of RIPK1 kinase activity and ubiquitylation of cFLIPL, respectively.

リンク情報
DOI
https://doi.org/10.1038/s42003-020-01603-y
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33469115
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815719
ID情報
  • DOI : 10.1038/s42003-020-01603-y
  • ORCIDのPut Code : 87097115
  • PubMed ID : 33469115
  • PubMed Central 記事ID : PMC7815719

エクスポート
BibTeX RIS