論文

査読有り
2012年11月

Protease Activity of Procaspase-8 Is Essential for Cell Survival by Inhibiting Both Apoptotic and Nonapoptotic Cell Death Dependent on Receptor-interacting Protein Kinase 1 (RIP1) and RIP3

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Mina Kikuchi
  • ,
  • Shunsuke Kuroki
  • ,
  • Mitsuhiro Kayama
  • ,
  • Shota Sakaguchi
  • ,
  • Kyung-Kwon Lee
  • ,
  • Shin Yonehara

287
49
開始ページ
41165
終了ページ
41173
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M112.419747
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Caspase-8 has an important role as an initiator caspase during death receptor-mediated apoptosis. Moreover, it has been reported to contribute to the regulation of cell fate in various types of cells including T-cells. In this report, we show that caspase-8 has an essential role in cell survival in mouse T-lymphoma-derived L5178Y cells. The knockdown of caspase-8 expression decreased the growth rate and increased cell death, both of which were induced by the absence of protease activity of procaspase-8. The cell death was associated with reactive oxygen species (ROS) accumulation, caspase activation, and autophagosome formation. The cell death was inhibited completely by treatment with ROS scavengers, but only partly by treatment with caspase inhibitors, expression of Bcl-xL, and knockdown of caspase-3 or Atg-7 which completely inhibits apoptosis or autophagosome formation, respectively, indicating that apoptosis and autophagy-associated cell death are induced simultaneously by the knockdown of caspase-8 expression. Further analysis indicated that RIP1 and RIP3 regulate this multiple cell death, because the cell death as well as ROS production was completely inhibited by not only treatment with the RIP1 inhibitor necrostatin-1, but also by knockdown of RIP3. Thus, in the absence of protease activity of procaspase-8, RIP1 and RIP3 simultaneously induce not only nonapoptotic cell death conceivably including autophagic cell death and necroptosis but also apoptosis through ROS production in mouse T-lymphoma cells.

Web of Science ® 被引用回数 : 28

リンク情報
DOI
https://doi.org/10.1074/jbc.M112.419747
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23071110
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000311887600032&DestApp=WOS_CPL

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