2024年10月1日 · We examined the role of GCN2 and the phosphorylation of eIF2α in regulating protein synthesis in the ire1a ire1b double mutants, finding that suppression of GCN2 expression and the introduction of a non-phosphorylatable variant of eIF2α only partially mitigated protein synthesis inhibition under ER stress (Fig. 5, Fig. 6). Although not as ...

2016年4月7日 · IRE1α has been known to splice X-box binding protein 1 (XBP1) mRNA, which is induced by ATF6 under ER stress. This spliced XBP1 mRNA is translated into the active transcription...

(IRE1a) branch of the unfolded protein response (UPR). This adaptation enables the cells to overcome their reliance on oncogenic KRAS, enhancing their resis-tance to KRASi (Figure 1). This insight underscores the complex interplay be-tween oncogenic signaling and protein quality control in scenarios of drug resis-tance.

2024年10月16日 · IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in Trp53−/− TNBC allows taxane to induce extensive dsRNAs that are sensed by ZBP1, which in turn activates NLRP3-GSDMD-mediated pyroptosis.

2020年8月8日 · p-IRE1α接下来会催化一个重要的过程：使Xbp1 mRNA发生剪切，形成一个功能活跃的转录因子Xbp1s。 Xbp1s进入细胞核后会启动一系列基因转录 (如脂质合成、ERAD等)，从多个层次缓解内质网应激。 除此之外p-IRE1α可以通过RIDD过程促进mRNA的降解，减缓新生多肽链合成，降低内质网压力。 （这个过程是不是很像学校（内质网）丧心病狂的把幼儿园的小孩（mRNA）全灭了，来年肯定没有新生（多肽链）入学了，学校可以专心收拾现有的学生了） …

In this study, the role of IRE1, a key component of the UPR, was investigated in protein translation regulation under ER stress conditions in Arabidopsis. We discovered that the loss of IRE1A and IRE1B leads to diminished protein translation, indicating a significant role for IRE1 in this process.

Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2a) are activated in stressed cells and negatively regulate protein syn-thesis. Phenotypic analysis of targeted mutations in murine cells reveals a novel role for eIF2 kinases.

整合应激反应 (integrated stress response, ISR) 是指氧化应激、氨基酸不足、内质网应激和未折叠蛋白积累等情况下, GCN2, PKR, PERK和 HRI 等4个关键激酶通过诱导真核细胞起始因子2(eIF2α)磷酸化以及转录因子4(ATF4) 活化介导的细胞适应性反应。

2024年7月23日 · 在这项研究中，研究了 IRE1 是 UPR 的关键组分，在拟南芥 ER 应激条件下的蛋白质翻译调节中的作用。 我们发现 IRE1A 和 IRE1B 的缺失导致蛋白质翻译减少，表明 IRE1 在此过程中起重要作用。 然而，这种调节并不仅仅取决于与 bZIP60 的相互作用，bZIP60 是 UPR 中的一个关键转录因子。 有趣的是，虽然化学伴侣 TUDCA 和 PBA 有效缓解了在 ire1a ire1b 突变体中观察到的翻译抑制，但这种效果比通过抑制 GCN2 表达或引入不可磷酸化的 eIF2α 变体观察 …

2022年5月6日 · In this study, transcriptome and lipidome profiling of triple negative breast cancer cells subjected to pharmacological inhibition of IRE1α reveals changes in lipid metabolism genes associated with...