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Review
. 2011 Apr;63(4):233-9.
doi: 10.1002/iub.433. Epub 2011 Mar 24.

Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

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Free article
Review

Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

Shinichi Kondo et al. IUBMB Life. 2011 Apr.
Free article

Abstract

The endoplasmic reticulum (ER) plays role in the maintenance of numerous aspects of cellular and organismal homeostasis by folding, modifying, and exporting nascent secretory and transmembrane proteins. Failure of the ER's adaptive capacity results in accumulation of unfolded or malfolded proteins in the ER lumen (ER stress). To avoid cellular damage, mammalian cells activate the specific signals from the ER to the cytosol or nucleus to enhance the capacity for protein folding, attenuate the synthesis of proteins, and degrade unfolded proteins. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins, PERK, IRE1, and ATF6. These ER stress transducers basically play important roles in cell survival after ER stress. Recently, novel types of ER stress transducers, OASIS family members that share a region of high sequence similarity with ATF6 have been identified. They have a transmembrane domain, which allows them to associate with the ER, and possess a transcription-activation domain and a bZIP domain. OASIS family proteins include OASIS, BBF2H7, CREBH, AIbZIP, and Luman. Despite the structural similarities among OASIS family proteins and ATF6, differences in activating stimuli, tissue distribution, and response element binding indicate specialized functions of each member on regulating the UPR in the specific organs and tissues. Here, we summarize our current understanding of biochemical characteristics and in vivo functions of OASIS family proteins, particularly focusing on OASIS and BBF2H7. A growing body of new works suggests that the UPR branches regulated by OASIS family members play essential roles in cell differentiation and maturation or maintenance of basal cellular homeostasis in mammals.

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