J. Biochem, 2004, Vol. 136, No. 3 343-350
© 2004 The Japanese Biochemical Society
MOLECULAR BIOLOGY |
Differential Contributions of ATF6 and XBP1 to the Activation of Endoplasmic Reticulum Stress-Responsive cis-Acting Elements ERSE, UPRE and ERSE-II
1 Graduate School of Biostudies, Kyoto University, Kyoto 606-8502; 2 Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502; 3 PRESTO, Japan Science and Technology Corporation, Saitama 332-0012; 4 National Cardiovascular Center Research Institute, Osaka 565-8565; 5 Howard Hughes Medical Institute; and 6 Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
ATF6 and XBP1 are transcription factors activated specifically in response to endoplasmic reticulum (ER) stress. Three cis-acting elements capable of binding to ATF6, XBP1 or both have been identified to date, namely ER stress–response element (ERSE), unfolded protein response element (UPRE) and ERSE-II. ERSE controls the expression of ER-localized molecular chaperones such as BiP that can refold unfolded proteins in the ER; transcription from ERSE is fully activated by ATF6 even in the absence of XBP1. In contrast, transcription from UPRE depends solely on XBP1 and it has been suggested that UPRE may control the expression of components of the ER-associated degradation system that can degrade unfolded proteins in the ER. The Herp gene, one of the most highly inducible genes under ER stress, encodes an ER membrane protein containing a ubiquitin-like domain with unknown functions, and carries ERSE-II in addition to ERSE in its promoter. In this report, we show that ERSE-II allows the NF-Y–dependent binding of ATF6 as in the case of ERSE and NF-Y–independent binding of XBP1 as in the case of UPRE, and that transcription from ERSE-II is mitigated in the absence of XBP1. Accordingly, the induction of Herp mRNA was diminished in the absence of XBP1 whereas that of BiP mRNA was not affected. These results may help in understanding the role of Herp in the quality control system in the ER.
* To whom correspondence should be addressed. Tel: +81-75-753-4067, Fax: +81-75-753-3718, E-mail: kazu.mori{at}bio.mbox.media.kyoto-u.ac.jp
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