論文

査読有り
2000年9月

ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response

MOLECULAR AND CELLULAR BIOLOGY
  • H Yoshida
  • ,
  • T Okada
  • ,
  • K Haze
  • ,
  • H Yanagi
  • ,
  • T Yura
  • ,
  • M Negishi
  • ,
  • K Mori

20
18
開始ページ
6755
終了ページ
6767
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/MCB.20.18.6755-6767.2000
出版者・発行元
AMER SOC MICROBIOLOGY

Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by the cis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREE5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N-9-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1.

リンク情報
DOI
https://doi.org/10.1128/MCB.20.18.6755-6767.2000
J-GLOBAL
https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902125874595291
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000088979100014&DestApp=WOS_CPL
ID情報
  • DOI : 10.1128/MCB.20.18.6755-6767.2000
  • ISSN : 0270-7306
  • J-Global ID : 200902125874595291
  • Web of Science ID : WOS:000088979100014

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