A time-dependent phase shift in the mammalian unfolded protein response

被引：591

作者：

Yoshida, H

Matsui, T

Hosokawa, N

Kaufman, RJ

Nagata, K

Mori, K ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Biostudies, Kyoto 6068304, Japan

[2] Kyoto Univ, Inst Frontier Med Sci, Dept Mol & Cellular Biol, Kyoto 6068397, Japan

[3] Univ Michigan, Med Ctr, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI 48109 USA

来源：

DEVELOPMENTAL CELL | 2003年 / 4卷 / 02期

关键词：

D O I：

10.1016/S1534-5807(03)00022-4

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Unfolded or misfolded proteins in the endoplasmic reticulum (ER) must be refolded or degraded to maintain homeostasis of the ER. The ATF6 and IRE1-XBP1 pathways are important for the refolding process in mammalian cells; activation of these transcriptional programs culminates in induction of ER-localized molecular chaperones and folding enzymes. We show here that degradation of misfolded glycoprotein substrates requires transcriptional induction of EDEM (ER degradation-enhancing (x-mannosidase-like protein), and that this is mediated specifically by IRE1-XBP1 and not by ATF6. As XBP1 is produced after ATF6 activation, our results reveal a time-dependent transition in the mammalian unfolded protein response: an ATF6-mediated unidirectional phase (refolding only) is followed by an XBP1-mediated bidirectional phase (refolding plus degradation) as the response progresses.

引用

页码：265 / 271

页数：7