荷兰癌症研究所William James Faller团队近期取得重要工作进展，他们研究提出，P-stalk核糖体是细胞因子介导过程的主调节器。相关研究成果2024年10月21日在线发表于《细胞》杂志上。
据介绍，炎性细胞因子对免疫反应至关重要。细胞因子暴露后，细胞进入“警戒状态”，增强其对免疫系统的可见性。
研究人员鉴定出了一个由P-stalk的存在定义的核糖体警报状态亚群。研究人员发现，P-stalk核糖体（PSR）是在与肿瘤免疫相关的细胞因子的作用下形成的，这至少部分是由P-stalk磷酸化介导的。PSR通过更有效地翻译参与细胞因子介导过程的受体分子的跨膜结构域，参与对细胞因子反应至关重要的mRNA的优先翻译。
重要的是，PSR的缺失会抑制CD8+ T细胞的识别和杀伤，而转化生长因子β（TGF-β）等抑制性细胞因子会阻碍PSR的形成，这表明PSR是多种信号汇聚的中心调节枢纽。因此，PSR是细胞因子暴露后通过翻译调节这一过程发生的细胞重新连接的重要介质。
附：英文原文
Title: P-stalk ribosomes act as master regulators of cytokine-mediated processes
Author: Anna Dopler, Ferhat Alkan, Yuval Malka, Rob van der Kammen, Kelly Hoefakker, Daniel Taranto, Naz Kocabay, Iris Mimpen, Christel Ramirez, Elke Malzer, Olga I. Isaeva, Mandy Kerkhoff, Anastasia Gangaev, Joana Silva, Sofia Ramalho, Liesbeth Hoekman, Maarten Altelaar, Roderick Beijersbergen, Leila Akkari, Jonathan Wilson Yewdell, Pia Kvistborg, William James Faller
Issue&Volume: 2024-10-21
Abstract: Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an “alert state” that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk. We show that P-stalk ribosomes (PSRs) are formed in response to cytokines linked to tumor immunity, and this is at least partially mediated by P-stalk phosphorylation. PSRs are involved in the preferential translation of mRNAs vital for the cytokine response via the more efficient translation of transmembrane domains of receptor molecules involved in cytokine-mediated processes. Importantly, loss of the PSR inhibits CD8+ T cell recognition and killing, and inhibitory cytokines like transforming growth factor β (TGF-β) hinder PSR formation, suggesting that the PSR is a central regulatory hub upon which multiple signals converge. Thus, the PSR is an essential mediator of the cellular rewiring that occurs following cytokine exposure via the translational regulation of this process.
DOI: 10.1016/j.cell.2024.09.039
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01139-5