論文

査読有り
2016年8月

The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction

ELIFE
  • Shun Koizumi
  • ,
  • Taro u Irie
  • ,
  • Shoshiro Hirayama
  • ,
  • Yasuyuki Sakurai
  • ,
  • Hideki Yashiroda
  • ,
  • Isao Naguro
  • ,
  • Hidenori Ichijo
  • ,
  • Jun Hamazaki
  • ,
  • Shigeo Murata

5
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.7554/eLife.18357
出版者・発行元
ELIFE SCIENCES PUBLICATIONS LTD

In response to proteasome dysfunction, mammalian cells upregulate proteasome gene expression by activating Nrf1. Nrf1 is an endoplasmic reticulum-resident transcription factor that is continually retrotranslocated and degraded by the proteasome. Upon proteasome inhibition, Nrf1 escapes degradation and is cleaved to become active. However, the processing enzyme for Nrf1 remains obscure. Here we show that the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is required to cleave and activate Nrf1. Deletion of DDI2 reduced the cleaved form of Nrf1 and increased the full-length cytosolic form of Nrf1, resulting in poor upregulation of proteasomes in response to proteasome inhibition. These defects were restored by adding back wild-type DDI2 but not protease-defective DDI2. Our results provide a clue for blocking compensatory proteasome synthesis to improve cancer therapies targeting proteasomes.

リンク情報
DOI
https://doi.org/10.7554/eLife.18357
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27528193
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000383866800001&DestApp=WOS_CPL
ID情報
  • DOI : 10.7554/eLife.18357
  • ISSN : 2050-084X
  • PubMed ID : 27528193
  • Web of Science ID : WOS:000383866800001

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