2024年6月1日 · In response to cellular stress, GCN1 orchestrates the activation of GCN2, thereby initiating subsequent ISR pathways crucial for maintaining cellular homeostasis. Moreover, GCN1 assumes a pivotal role in the quality control mechanisms associated with ribosomes, collaborating with other factors to efficiently address ribosome collision events ...

2021年3月31日 · Here we illustrate how a single protein can monitor both ribosomes within a disome, by presenting a cryo-electron microscopy structure of a native complex of the ISR protein Gcn1 interacting with both the leading stalled ribosome and the following colliding ribosome.

A recent mouse knockout study has provided added insights regarding the relationship between GCN1 and GCN2. As expected, GCN1 KO mouse fibroblasts could not induce ISR in response to amino acid deprivation. In addition, GCN1 KO mice exhibited additional developmental defects not found in GCN2 null mice . These results are consistent with the ...

2024年12月25日 · GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (By similarity). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF ...

2023年6月19日 · GCN1 was initially shown to sense uncharged tRNAs at the ribosome A-site upon amino acid starvation, resulting in eIF2α phosphorylation via GCN2 kinase 26 and global downregulation of translation as part of the integrated stress response (ISR). 27 More recently, this function was linked to GCN1 binding to collided ribosomes (disomes) upon ...

2021年4月1日 · The Gcn pathway is conserved in all eukaryotes, including mammals such as humans, where it is a crucial part of the integrated stress response (ISR). Gcn1 serves as an essential effector protein for the kinase Gcn2, which in turn is activated by stalled ribosomes, leading to phosphorylation of eIF2 …

2020年4月23日 · Here, we show that GCN1 is involved in GCN2-mediated eIF2α phosphorylation after AAS and UV radiation by generating Gcn1 mutant mice. Interestingly, GCN1 not only regulates the eIF2α-mediated stress response but also the cell cycle and cell proliferation in a GCN2-independent manner.

2024年11月19日 · Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4.

2024年3月5日 · The GCN1–GCN2 pathway mediates the integrated stress response (ISR). In response to various stressors, eIF2α phosphorylation by stress-specific kinases attenuates global translation initiation, which is known as ISR and is conserved in eukaryotes (right part).

2025年2月18日 · 解码无功能的核糖体通过空缺的A位点触发GCN2依赖的eIF2α磷酸化，激活胁迫反应（ISR），但不引起核糖体碰撞。 GCN1优先结合这些解码无功能的核糖体，增强GCN2介导的翻译抑制。 六. GCN2通过精细调节翻译起始确保18S NRD. 研究表明，解码无功能的核糖体通过GCN2依赖的eIF2⍺磷酸化减少翻译起始，促进18S NRD。