GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress.

Recombinant protein containing the carboxyl-terminal domain from wild-type GCN2 was found to bind dsRNA, whereas no association was found with Sepharose alone. The recombinant gcn2-605 protein had no affinity for dsRNA. We conclude that the ribosomal targeting domain of GCN2 can bind dsRNA.

2024年7月1日 · GCN2 can sense viral infections through various avenues. Viruses utilise multiple avenues to counteract or exploit GCN2 and the GCN2 pathway. Knowledge on molecular mechanisms holds promise for new anti-viral measures. Viral mechanisms may be exploited for non-communicable disease treatment and more.

2023年9月20日 · GCN2是在所有真核生物中发现的最进化保守的eIF2AK，其功能是通过调节细胞类型特异性功能来调节生理和病理进程，包括代谢、免疫、癌症等。 与此同时一些证据表明GCN2在调节巨噬细胞（Mφ）功能中起着关键作用，GCN2的缺失导致腹膜Mφ对dsDNA病毒感染的易感性增加。 Mφ在调节红细胞（RBCs）的产生和清除之间的平衡方面也发挥着核心作用，尤其对于在急性失血或溶血等应激条件下促进红细胞的生产。 红细胞在骨髓（BM）中的红细胞 …

整合应激反应 （integrated stress response ISR）是蛋白质稳态失调时诱发的信号中心调控网络，主要以控制蛋白质合成速率来实现。 2020年4月24日，美国贝勒医学院的 Mauro Costa-Mattioli 和UCSF大学的 Peter Walter 在 Science 上发表题为 The integrated stress response: From mechanism to disease 综述。 本综述总结了ISR调控机制以及ISR异常时如何导致复杂疾病发生，包括认知障碍、神经退行性疾病、肿瘤和糖尿病等。 最后作者指出开发出调控ISR的有效药 …

2014年5月23日 · GCN2 is a multidomain protein with key regulatory domains that directly monitor uncharged tRNAs which accumulate during nutrient limitation, leading to activation of this eIF2 kinase and translational control. A critical feature of regulation of this stress response kinase is its C-terminal domain (CTD).

The IFN-induced double-stranded RNA-dependent protein kinase (PKR) is one of the four mammalian serine-threonine kinases (the three others being HRI, GCN2 and PERK) that phosphorylate the eIF2 alpha translation initiation factor, in response to stress signals, mainly as a result of viral infections. …

2020年8月13日 · To examine whether GCN2 dampens DENV virion formation by interfering with its replication, we assessed the intracellular accumulation of DENV double stranded (dsRNA) intermediate through confocal microscopy using J2 antibody, which specifically detects dsRNA but not tRNA or cellular rRNA, and has been previously used to detect Flavivirus ...

2024年1月28日 · 有两种机制可以触发应激期间 GCN2 激活的有序过程： GCN2 通过积累不带电的 tRNA 或通过停滞和碰撞的核糖体来监测应激。 我们的结果表明，虽然核糖体碰撞确实对响应翻译延伸抑制剂的 GCN2 激活至关重要，但触发 tRNA 脱酰化的条件通过与受影响的 tRNA 的直接结合激活 GCN2。 两种机制都需要与组氨酸 tRNA 合成酶相关的 GCN2 调节结构域。 紫外线照射激活的 GCN2 具有氨基酸降低、未带电的 tRNA 增加和紫外线诱导的核糖体碰撞的特点，被认为 …

GCN2 (general control nonderepressible 2), a stress response kinase, plays a key role in sensing and modulating the response to amino acid deprivation. GCN2 activation in T cells leads to an induction of the integrated stress response pathway and …