Fine-Tuning of the Unfolded Protein Response: Assembling the IRE1α Interactome

被引:334
作者
Hetz, Claudio [1 ,2 ,3 ]
Glimcher, Laurie H. [3 ,4 ]
机构
[1] Univ Chile, Fac Med, Inst Biomed Sci, FONDAP Ctr Mol Studies Cell, Santiago, Chile
[2] Univ Chile, Millennium Nucleus Neural Morphogenesis NEMO, Santiago, Chile
[3] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR XBP-1; PLASMA-CELL DIFFERENTIATION; ER-STRESS; BAX INHIBITOR-1; MESSENGER-RNA; INDUCED APOPTOSIS; SENSOR IRE1-ALPHA; BIPOLAR DISORDER; LUMINAL DOMAIN;
D O I
10.1016/j.molcel.2009.08.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endoplasmic reticulum (ER) stress is a hallmark feature of secretory cells and many diseases, including cancer, neurodegeneration, and diabetes. Adaptation to protein-folding stress is mediated by the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). The UPR signals through three distinct stress sensors located at the ER membrane-IRE1 alpha, ATF6, and PERK. Although PERK and IRE1 alpha share functionally similar ER-luminal sensing domains and both are simultaneously activated in cellular paradigms of ER stress in vitro, they are selectively engaged in vivo by the physiological stress of unfolded proteins. The differences in terms of tissue-specific regulation of the UPR may be explained by the formation of distinct regulatory protein complexes. This concept is supported by the recent identification of adaptor and modulator proteins that directly interact with IRE1 alpha. In this Review, we discuss recent evidence supporting a model where IRE1 alpha signaling emerges as a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble.
引用
收藏
页码:551 / 561
页数:11
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