Activation of mammalian IRE1α upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins
被引:149
作者:
Oikawa, Daisuke
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, JapanRIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan
Oikawa, Daisuke
[1
]
论文数: 引用数:
h-index:
机构:
Kimata, Yukio
[2
]
论文数: 引用数:
h-index:
机构:
Kohno, Kenji
[2
]
Iwawaki, Takao
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan
Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, JapanRIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan
Iwawaki, Takao
[1
,3
]
机构:
[1] RIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan
[2] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300192, Japan
[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
IRE1, an ER-localized transmembrane protein, plays a central role in the unfolded protein response. Upon ER stress, IRE1 senses the accumulation of unfolded proteins in the ER, and transfers signal from the ER to the cytosol. Recently, it was reported that the luminal domain of yeast Ire1 senses the unfolded proteins via a two-step mechanism, namely dissociation of BiP and direct interaction with unfolded proteins. However, it has been unclear whether a similar mechanism is applicable to mammalian IRE1 alpha. To address this point, we analyzed luminal-domain mutants of mammalian IRE1a in cells, and evaluated the anti-aggregation activity of the luminal fragment of IRE1a in vitro. We generated a mutant that has low affinity for BiP, and this mutant was significantly activated even under normal conditions. Moreover, the luminal fragments of mammalian IRE1a did not exhibit anti-aggregation activity. These results suggest that in contrast to yeast Ire1, the regulation of mammalian IRE1a strongly depends on the dissociation of BiP. (C) 2009 Elsevier Inc. All rights reserved.
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Credle, JJ
;
Finer-Moore, JS
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Finer-Moore, JS
;
Papa, FR
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Papa, FR
;
Stroud, RM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Stroud, RM
;
Walter, P
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
机构:
RIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, JapanRIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, Japan
Iwawaki, Takao
;
Akai, Ryoko
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, JapanRIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, Japan
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Credle, JJ
;
Finer-Moore, JS
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Finer-Moore, JS
;
Papa, FR
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Papa, FR
;
Stroud, RM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Stroud, RM
;
Walter, P
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA
机构:
RIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, JapanRIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, Japan
Iwawaki, Takao
;
Akai, Ryoko
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, JapanRIKEN, Iwawaki Initiat Res Unit, Frontier Res Syst, Wako, Saitama 3510198, Japan