Programmed death ligand 1 (PD-L1) is critical for the ability of cancer cells to evade attacks by the host immune system. However, the molecular mechanisms controlling PD-L1 expression have not been fully understood. Here, we demonstrate that sorting nexin 6 (SNX6) is a novel regulator of PD-L1 expression. Knockdown of SNX6 in cancer cells significantly decreases PD-L1 protein levels. In contrast, loss of SNX6 does not reduce PD-L1 mRNA levels. Instead, SNX6 interacts with Cullin3, an E3 ubiquitin ligase responsible for PD-L1 ubiquitination and subsequent degradation. By binding with Cullin3, SNX6 decreases the interaction between the adaptor protein speckle-type POZ protein and Cullin3, which in turn downregulates Cullin3-mediated PD-L1 ubiquitination. This research reveals a novel molecular nexus in modulating PD-L1.

中文翻译：

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排序 nexin 6 与 Cullin3 相互作用并调节程序性死亡配体 1 的表达

程序性死亡配体 1 (PD-L1) 对于癌细胞逃避宿主免疫系统攻击的能力至关重要。然而，控制 PD-L1 表达的分子机制尚未完全清楚。在这里，我们证明排序 nexin 6 (SNX6) 是 PD-L1 表达的新型调节器。敲除癌细胞中的 SNX6 会显着降低 PD-L1 蛋白水平。相反，SNX6 的缺失不会降低 PD-L1 mRNA 水平。相反，SNX6 与 Cullin3 相互作用，Cullin3 是一种 E3 泛素连接酶，负责 PD-L1 泛素化和随后的降解。通过与 Cullin3 结合，SNX6 降低了衔接蛋白斑点型 POZ 蛋白与 Cullin3 之间的相互作用，进而下调了 Cullin3 介导的 PD-L1 泛素化。这项研究揭示了调节 PD-L1 的新分子关系。