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This action blocks downstream mRNA translation on a large scale, reducing the protein load on the ER ( 3.1.2 The inositol-requiring enzyme 1α signaling pathway When large quantities of misfolded proteins accumulate in the ER, IRE1α is oligomerized and activated ( 3.1.3 The activating transcription factor 6 signaling pathway ATF6, a single-pass type II transmembrane protein, has a cytoplasmic domain composed of 370–380 amino acids, followed by a 21-amino-acid transmembrane domain and a cytoplasmic domain of 270 amino acids projecting into the ER lumen ( ER stress is essentially a protective mechanism that reduces new protein production to alleviate the ER burden and prevent the accumulation of unfolded proteins (57)