2021年5月14日 · Our findings demonstrated that dysfunctional GCN2 enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary vascular wall.

2024年8月27日 · Drainas et al. identify GCN2 as a factor influencing small-cell lung cancer (SCLC) response to the WEE1 inhibitor AZD1775. AZD1775 directly activates the GCN2 stress response pathway, increasing its effectiveness in killing SCLC cells. Thus, activating the GCN2 pathway presents a novel opportunity to enhance WEE1 inhibitor efficacy in SCLC.

Our findings demonstrated that dysfunctional GCN2 enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary vascular wall.

2023年4月1日 · In this study, we report that one such Gcn2 inhibitor, Gcn2iB, can activate Gcn2, and we probe the mechanism by which this activation occurs. Low concentrations of Gcn2iB increase Gcn2 phosphorylation of eIF2 and enhance Atf4 expression and activity.

2007年2月7日 · GCN2 is a sensor of amino acid deprivation that triggers a repression of global protein synthesis while simultaneously inducing translation of specific proteins. In this issue of Cell Metabolism, Guo and Cavener (2007) present a much broader role for GCN2 in controlling lipid homeostasis in response to amino acid deprivation.

2016年6月14日 · Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity,...

Cellular α-KG levels can be regulated by phosphoserine aminotransferase1 (Psat1), which is an Oct4/Sox2/Nanog target protein. Decreased expression of Psat1 in mESCs lowers the levels of DNA 5’-hydroxymethylcytosine and H3K9me3, resulting in accelerated differentiation of mESCs (Hwang et al., 2016 ).

2018年2月14日 · Different conditions can stimulate amino acid deprivation and increase levels of uncharged tRNA, which activate the amino acid sensor GCN2. This represents a checkpoint whereby cells irrevocably...

在这项最新研究中，研究团队发现，使用GCN2激动剂halofuginone（halo）在体外激活效应性CD8+ T细胞的氨基酸饥饿反应，可以增强其氧化代谢和效应器功能。 从机制上来说，该研究确定了自噬与CD98-mTOR信号轴是halo治疗所诱导的表型的关键下游介质。 将halo处理的CD8+ T细胞过继转移到荷瘤小鼠模型中，导致了强大的肿瘤控制和治愈反应。 在体内，halo处理的T细胞与4-1BB激动性抗体协同作用，在免疫治疗耐药的小鼠模型中抑制了肿瘤生长。 重要的是，使 …

GCN2（General control nonderessible 2）是一种 eIF2α 激酶，当细胞处于氨基酸饥饿应激下时，它负责完全重新连接细胞的代谢。 最近，人们对 GCN2 作为潜在肿瘤靶点重新产生了兴趣，多项研究报告了小分子抑制剂的开发。