2020年11月2日 · To better understand a role of eIF4E S209 in oncogenic translation, we generated EIF4ES209A/+ heterozygous knockin (4EKI) HCT 116 human colorectal cancer (CRC) cells. 4EKI had little impact on total eIF4E levels, cap binding or global translation, but markedly reduced HCT 116 cell growth in spheroids and mice, and CRC organoid growth. 4EKI stron...

2020年11月2日 · Using EIF4E S209A/+ knockin (4EKI) human colon cancer cells and mice, human CRC organoids and adenoma samples, we uncovered a key role of p-4E in Myc and ATF4 translation, which promotes ISR-dependent glutamine …

2010年8月2日 · Ser209 Is the Only Phosphorylation Site in eIF4E. To address the role of eIF4E phosphorylation in tumorigenesis, a knock-in (KI) mouse in which serine 209 was replaced by an alanine residue was generated. The strategy and targeting vector construction for the generation, selection, and genotyping of the S209A mice is shown in Fig. S1.

Using EIF4E S209A/+ knockin (4EKI) human colon cancer cells and mice, human CRC organoids and adenoma sam-ples, we uncovered a key role of p-4E in Myc and ATF4 translation, which promotes ISR-dependent glutamine metabolism, AKT signaling and oncogenic proliferation.

2020年11月2日 · 为了更好地了解 eIF4E S209 在致癌翻译中的作用，我们生成了 EIF4ES209A/+ 杂合敲入 (4EKI) HCT 116 人结直肠癌 (CRC) 细胞。 4EKI 对总 eIF4E 水平、帽结合或全局翻译几乎没有影响，但显着降低了球体和小鼠的 HCT 116 细胞生长以及 CRC 类器官的生长。 4EKI 强烈抑制 Myc 和 ATF4 翻译、综合应激反应 (ISR) 依赖性谷氨酰胺代谢特征、AKT 激活和体内增殖。 4EKI 通过抑制 Myc 蛋白和 AKT 激活来抑制 ApcMin/+ 小鼠的息肉病。 此外，p-eIF4E 在小鼠 …

Rapamycin and its analogs increased eIF4E(S209) phosphorylation at S209, despite no direct activation site for rapamycin on this protein (36–38). We now show that the effects of both RAD001 and bicalutamide on eIF4E phosphorylation are mediated by increased activation of the MAPK pathway which regulates Mnk1/2, the kinase that phosphorylates ...

eIF4E磷酸化的结果出现的一个关键特征是磷酸化的S209（pS209）与eIF4E帽结合界面中特定的赖氨酸残基对（K159和K162）之间的盐桥网络。 这种相互作用使蛋白质的动态C端区域稳定下来，导致装订袋的整体可塑性和可及性下降。

2017年11月16日 · We confirmed using a human-derived tumor xenograft mouse model that bicalutamide pre-treatment is associated with an increase in eIF4E (S209) phosphorylation. Thus, AR suppressed eukaryotic initiation factor 4E (eIF4E) phosphorylation, while the use of antiandrogens relieved this suppression, thereby triggering its increase.

The mRNA cap-binding oncoprotein "eIF4E" is phosphorylated at residue S209 by Mnk kinases, and is closely associated with tumor development and progression. Despite being well-established, mechanistic details at the molecular level of mRNA recognition by eIF4E due to phosphorylation have not been cl …

2021年2月2日 · Mutational activation of Wnt/Myc and RAS signaling promotes colorectal cancer (CRC) development and deregulates translation. Phosphorylation of the cap binding protein eIF4E (Serine 209) is commonly elevated in cancer such as …