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 …

General control nonderepressible 2 (GCN2), which is encoded by eukaryotic translation initiation factor 2 alpha (eIF-2α) kinase 4 (EIF2AK4), is a serine/threonine-protein kinase that senses amino acid deficiencies through binding to uncharged transfer RNA (tRNA).

2023年12月5日 · Herein, we identify a novel amino-acid-sensing mechanism of mTORC1 that utilizes uncharged transfer RNA (tRNA)-mediated general control nonderepressible 2 (GCN2) activation to augment the F-box only protein 22 (FBXO22) activity for mTOR ubiquitination and mTORC1 inhibition.

2024年7月1日 · Another mechanism of GCN2 activation is by viral RNA binding to the HisRS-like domain of GCN2 (Figure 3 c). Analogous to uncharged tRNAs binding to the HisRS-like domain, viral RNA can bind to this domain and lead to the stimulation of …

To determine the cell-intrinsic role of GCN2 in myeloid function, we conducted in vitro experiments characterizing the transcriptome by RNA-seq and DNA binding characteristics of its obligate downstream effector ATF4 in Mϕ and MDSC cultures. We also characterized GCN2-dependent effects on metabolism by RNA-seq, qPCR, and seahorse assay.

The blocking of early viral SV RNA translation by GCN2 inhibits SV replication, pointing out another important function of GCN2 in the cellular response to viruses. Upon yellow fever vaccination, activated GCN2 programs dendritic cells to promote stress granule formation and autophagy, and also increases antigen presentation to CD4 + and CD8 ...

2017年4月1日 · General control nonderepressible 2 (GCN2) is activated by the accumulation of uncharged tRNA in response to amino acid shortage and regulates amino acid starvation response in the cytosol. Here we report the nucleolar localization of GCN2 and the association between GCN2 and small RNA transcripts.

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.

2017年4月1日 · Our findings reveal a role of GCN2 in the nucleolus that is involved in the expression of small RNA transcripts and serves as alternative stress-sensing machinery for nutrient deficiency. Thus, GCN2 may play pivotal roles in multiple protein translation checkpoints in both the nucleolus and cytosol.

2024年6月6日 · GCN2 is a stress response kinase that phosphorylates the translation initiation factor eIF2α to inhibit general protein synthesis when activated by uncharged tRNA and stalled ribosomes.