RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:SUMOylation and related post-translational modifications in natural killer cell anti-cancer responses.
SUMOylation and related post-translational modifications in natural killer cell anti-cancer responses.
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SUMO化是一种可逆修饰,涉及将小泛素样修饰蛋白(SUMO)共价连接到靶蛋白上,从而导致其定位、功能、稳定性和相互作用谱发生变化。SUMO化及其他相关的翻译后修饰已成为多种生物过程的重要调节因子,包括基因组稳定性调控和免疫应答。自然杀伤(NK)细胞是先天免疫细胞,在宿主防御病毒感染和肿瘤中发挥关键作用。NK细胞无需预先致敏即可识别并杀伤感染或转化的细胞,其活性受到活化性和抑制性受体平衡的严格调控。NK细胞受体及其在靶细胞上的特异性配体的表达,在恶性转化过程中通过整合包括泛素化和泛素样翻译后修饰在内的不同机制而受到精细调控。本综述总结了SUMO化及其他相关通路在NK细胞生物学中的作用,特别强调其对肿瘤应答的调控。本文还简要讨论了新型选择性抑制剂的开发,作为增强NK细胞介导的肿瘤细胞杀伤的有用工具。
SUMOylation is a reversible modification that involves the covalent attachment of small ubiquitin-like modifier (SUMO) to target proteins, leading to changes in their localization, function, stability, and interactor profile. SUMOylation and additional related post-translational modifications have emerged as important modulators of various biological processes, including regulation of genomic stability and immune responses. Natural killer (NK) cells are innate immune cells that play a critical role in host defense against viral infections and tumors.
NK cells can recognize and kill infected or transformed cells without prior sensitization, and their activity is tightly regulated by a balance of activating and inhibitory receptors. Expression of NK cell receptors as well as of their specific ligands on target cells is finely regulated during malignant transformation through the integration of different mechanisms including ubiquitin- and ubiquitin-like post-translational modifications.
Our review summarizes the role of SUMOylation and other related pathways in the biology of NK cells with a special emphasis on the regulation of their response against cancer. The development of novel selective inhibitors as useful tools to potentiate NK-cell mediated killing of tumor cells is also briefly discussed.
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