2022年11月11日 · Our preliminary results demonstrate that metformin activates AMPK to reduce TG synthesis by inhibiting the XBP1-mediated DGAT2 pathway, at least in part, suggesting that XBP1 is a new metabolic mediator for metformin treatment of hypertriglyceridemia and associated metabolic disease.

2022年2月10日 · Genetic and pharmacological inhibition of Xbp1 specifically in hepatocytes ameliorated APAP-induced liver injury by enhancing autophagy and decreasing CYP2E1 expression. These findings provide...

2020年8月8日 · pPerk磷酸化下游的elF2，p-elF2可以促进转录因子ATF4翻译，ATF4功能与Xbp1s相似，通过启动一系列基因转录从多个层次缓解内质网应激。 内质网应激过于严重ATF4会启动chop的转录，chop启动促凋亡程序促进细胞凋亡。 3. ATF6通路： ATF6与GRP78/BiP分离后会从ER膜上掉下来，跑到高尔基体被蛋白酶裂解，生成转录因子ATF6p50。 进入细胞核中通过启动一系列基因转录从多个层次缓解内质网应激。 作者：SQW， 免疫学在读硕士生 ，专注肿 …

2018年12月10日 · Here we identified a signaling pathway—involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes 2, 3 —that was activated in...

研究人员验证了Xbp1s和Hspa5在Tm处理开始后的12和15小时最大程度地诱导，并在24小时后显着降低。 因此，当Xbp1s和Hspa5均被高度诱导（13小时）和表达水平减弱时（25小时）收获了细胞用于scRNA-seq。 结果显示在Tm处理后25小时，肠上皮细胞的相对比例有所降低。 进一步的研究发现，带来这一差异的并不是杯状细胞对细胞凋亡的内在抗性所致，而是杯状细胞有具有适应长时间ER应激的机制来抵御细胞凋亡。 最终，作者确定了192个终末UPR标志基因，包括18个 …

XBP1 deficiency abruptly increases apoptosis and autophagy, suggesting that XBP1 functions in moderating these events. Of note, we found that AMPK activation is increased in XBP1-knockdown cells. AMPK activation is enhanced by intracellular ATP depletion and is also involved in autophagy induction [ 45 , 46 ].

2016年1月18日 · Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that response, with...

2011年1月1日 · To examine the down-stream effectors of ER stress, we used a specific ER stress-induced protein X-box-binding protein 1 (XBP1) on AMPK activation. XBP1 is a key transcription factor that when spliced increases the expression of proteins that supply the ER with resident-folding assistants, thereby rebalancing protein load with increased folding ...

2022年11月11日 · 研究者进一步利用质谱流式技术分析发现，肿瘤细胞内XBP1的缺失减少了肿瘤微环境中髓系来源的免疫抑制性细胞（myeloid-derived suppressor cell，MDSC），增加了活化的CD8 T细胞。 为了深入理解肿瘤细胞中XBP1对肿瘤免疫的调节作用，研究者通过转录组测序和脂质组学分析发现，肿瘤细胞内XBP1的缺失造成了肿瘤组织中胆固醇水平降低，伴随着胆固醇合成途径中关键酶HMGCR转录水平的下降。 由于XBP1缺失可能造成IRE1α代偿性激活，而此前 …

AMP-activated protein kinase (AMPK) regulates the balance between cellular anabolism and catabolism dependent on energy resources to maintain proliferation and survival. Small-compound AMPK activators show anti-cancer activity in preclinical models.