Humeau Juliette, Bezu Lucillia, Kepp Oliver, Kroemer Guido
Equipe Labellisée Par La Ligue Contre Le Cancer, Université De Paris, Sorbonne Université, INSERM UMR1138, Centre De Recherche Des Cordeliers, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.
Mol Cell Oncol. 2020 Jun 19;7(5):1776570. doi: 10.1080/23723556.2020.1776570. eCollection 2020.
Different intrinsic and extrinsic stress pathways including endoplasmic reticulum (ER) stress converge on the phosphorylation of eukaryotic translation initiation factor 2A (EIF2A, best known as eIF2α), which characterizes the so-called "integrated stress response". This phosphorylation event is important for the induction of autophagy in response to multiple distinct stressors, as well as for the exposure of calreticulin (CALR) as an "eat me" signal on the surface of the plasma membrane of stressed cells. Both autophagy and CALR exposure are required for immunogenic cell death, a modality of cellular demise that ignites anticancer and antiviral immune responses. In several different cancer types, eIF2α phosphorylation indicates favorable prognosis, correlating with an enhanced antitumor immune response.
不同的内在和外在应激途径，包括内质网（ER）应激，都汇聚于真核生物翻译起始因子2A（EIF2A，通常称为eIF2α）的磷酸化，这一过程构成了所谓的“综合应激反应”。这种磷酸化事件对于响应多种不同应激源诱导自噬很重要，同时也有助于钙网蛋白（CALR）作为应激细胞质膜表面的“吃我”信号暴露出来。自噬和CALR暴露都是免疫原性细胞死亡所必需的，免疫原性细胞死亡是一种引发抗癌和抗病毒免疫反应的细胞死亡方式。在几种不同类型的癌症中，eIF2α磷酸化表明预后良好，与增强的抗肿瘤免疫反应相关。
