2024年11月26日 · Our findings highlight the coordinated interplay between GCN2 and p53 regulation during nutrient stress and provide insight into how they could be targeted in developing new therapeutic strategies for PCa. Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression.

2024年11月26日 · Loss of p53 renders PCa cells sensitive to GCN2 inhibition and enhances cell death, suggesting that GCN2 and the ISR intersect with the p53 tumor suppressor pathway to control PCa survival during nutrient limitation.

The nucleolar localization of GCN2 regulates small RNA transcripts, which may serve as alternative stress-sensing machinery for nutrient deficiency. Depletion of GCN2 by siRNA increases small RNA transcripts and induces activation of the p53 pathway, which is dependent on B-related factor 1 . 4. Biological Functions of GCN2

2024年7月3日 · 研究发现在 DNA 损伤治疗中， SLFN11 会关闭细胞的蛋白质工厂“核糖体”，使缺乏肿瘤蛋白 p53 （ TP53 ）的癌细胞仍可发生细胞凋亡。强调了核糖体停滞是 DNA 损伤影响细胞命运的信号事件。 文章索引 【题目】 DNA damage induces p53-independent apoptosis through ribosome stalling

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.

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.

2023年4月4日 · Induced G1 arrest and p53/p21 signaling by GCN2 inhibition is reversed by supplementation with EAAs, suggesting amino acid limitation is critical for activation of p53. Metabolic stresses, such as amino acid starvation, have been suggested to activate p53 in different cancers and p53 regulates metabolic pathways that are critical for cancer ...

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 …

Loss of p53 renders PCa cells sensitive to GCN2 inhibition and enhances cell death, suggesting that GCN2 and the ISR intersect with the p53 tumor suppressor pathway to control PCa survival during nutrient limitation.

Thus, upon GCN2 kinase activation, p53 increases and may contribute to both decreased proliferation and increased apoptosis. Interestingly, a previous study demonstrated that IDO, through TRP depletion and GCN2 kinase activation, increases p53 expression in human T-cells, resulting in a p53-dependent suppression of cell proliferation ( 13 ).