PDF(Pubmed)
Abstract：
Environmental and physiological situations can challenge the balance between protein synthesis and folding capacity of the endoplasmic reticulum (ER) and cause ER stress, a potentially lethal condition. The unfolded protein response (UPR) restores ER homeostasis or actuates programmed cell death (PCD) when ER stress is unresolved. The cell fate determination mechanisms of the UPR are not well understood, especially in plants. Here, we integrate genetics and ER stress profiling with natural variation and quantitative trait locus analysis of 350 natural accessions of the model species Arabidopsis thaliana. Our analyses implicate a single nucleotide polymorphism to the loss of function of the general PCD regulator BON-ASSOCIATED PROTEIN2 (BAP2) in UPR outcomes. We establish that ER stress-induced BAP2 expression is antagonistically regulated by the UPR master regulator, inositol-requiring enzyme 1 (IRE1), and that BAP2 controls adaptive UPR amplitude in ER stress and ignites pro-death mechanisms in conditions of UPR insufficiency.
摘要：
环境和生理状况可以挑战内质网（ER）的蛋白质合成和折叠能力之间的平衡，并引起内质网应激，潜在的致命疾病.当ER应激未解决时,未折叠蛋白应答(UPR)恢复ER稳态或启动程序性细胞死亡(PCD)。UPR的细胞命运决定机制尚不清楚，尤其是在植物中。这里,我们将遗传学和ER胁迫谱与350个模式物种拟南芥自然种质的自然变异和数量性状基因座分析相结合。我们的分析提示单核苷酸多态性与UPR结果中一般PCD调节因子BON相关蛋白2(BAP2)功能丧失有关。我们确定ER应激诱导的BAP2表达受UPR主调节因子的拮抗调节，需要肌醇的酶1（IRE1），并且BAP2控制内质网应激中的适应性UPR幅度，并在UPR不足的情况下点燃促死亡机制。
