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6月9日 · Endogenous GCN2 was knocked down with siRNA in HeLa cells, HeLa cells expressing GCN2‐siR or GCN2‐siR‐AAXA. Progression from prophase to anaphase was observed by live‐cell imaging. Averages and SEM from three independent experiments are …

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.

2022年10月27日 · We demonstrate that restricting glutamine utilization in tumor cells induces a GCN2-dependent signaling pathway leading to TRAIL-R2 upregulation that together with GCN2-independent FLIP...

2022年4月25日 · Halofuginone (HF) is a phase 2 clinical compound that inhibits the glutamyl‐prolyl‐tRNA synthetase (EPRS) thereby inducing the integrated stress response (ISR). Here, we report that halofuginone indeed triggers the predicted canonical ISR adaptations, consisting of attenuation of protein synthesis and gene expression reprogramming.

2024年7月1日 · In one such example, in Henrietta Lacks (HeLa) P4 cells, the knockdown of GCN2 via small inhibitory RNA silencing (siRNA) leads to an almost 2-fold increase in infectivity to Human Immunodeficiency Virus 1 (HIV-1). 13 Furthermore, as one would expect, overexpression of functional GCN2 in NIH 3T3 cells (a MEF cell line) severely reduces the ...

GCN2 was a critical driver of Mϕ polarization and immunosuppression within the TME by promoting translation of the CREB-2/ATF4 transcription factor. GCN2 activity negatively correlated with antitumor responses and overall survival in human melanoma, suggesting further study into therapeutic targeting of this gene.

2021年12月3日 · Treatment with GCN2 siRNA suppressed the expression of ATF4 and REDD1 in the absence of glutamine or arginine in the medium (Fig. 2D). These data suggest that the GCN2/ATF4 pathway is important...

2018年3月22日 · Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α.

2017年4月1日 · We found that siRNA-mediated depletion of GCN2 increases small RNA transcripts such as tRNA and 5S rRNA, and induces the p53 pathway activation. Derepression of these transcripts and p53 pathway activation by GCN2 depletion was restored by depletion of B-related factor 1 (BRF1), a primary subunit of RNA polymerase III (pol III) components.