PD-L1(CD274)糖基化和转位至细胞膜
中文名称
通路描述
PD-L1(CD274)的糖基化在决定其蛋白质功能和稳定性方面发挥关键作用。该蛋白在ER腔内由OST复合物在N192、N200和N219位点进行N-糖基化。此过程对于PD-L1的稳定性至关重要，并抑制其被GSK3B靶向进行泛素-蛋白酶体降解（Li et al., 2016）。此外，由IL6通路激活的JAK1正调节糖基化过程，通过协助招募内质网关联的N-糖基转移酶STT3A（OST复合物的一部分）来催化PD-L1的糖基化（Chan et al., 2019）。PD-L1在Tyr112（Y112）位点被IL6-激活的JAK1磷酸化。此过程有助于稳定PD-L1蛋白。在ER腔内糖基化后的PD-L1被转运至高尔基复合体，在那里由B3GNT3进行进一步糖基化（Li et al., 2018）和由MIB2介导的K63泛素化（Yu et al., 2023）。高尔基体后，PD-L1被转运至细胞膜，在那里它可以与其受体结合并诱导免疫耐受。
英文描述
PD-L1(CD274) glycosylation and translocation to plasma membrane PD-L1 (CD274) glycosylation plays a critical role in determining the protein function and stability. PD-L1 is N-glycosylated at N192, N200 and N219 by the OST complex in the ER lumen. This process is important for PD-L1 stability and inhibits its targeting for proteasomal degradation by GSK3B (Li et al., 2016). Also, JAK1 activated by IL6 pathway positively regulates the glycosylation process by aiding in the process of recruiting endoplasmic reticulum-associated N-glycosyltransferase STT3A (part of the OST complex) to catalyse PD-L1 glycosylation (Chan et al., 2019). PD-L1 is phosphorylated by IL6-activated JAK1 at Tyr112 (Y112). This process aids in stabilizing the PD-L1 protein. PD-L1, once glycosylated in the ER lumen, get translocated to the Golgi complex for further glycosylation by B3GNT3 (Li et al., 2018) and K63-ubiquitination by MIB2 (Yu et al., 2023). Post Golgi, PD-L1 gets transported to the plasma membrane where it can bind with its receptor and induce immune tolerance.
所含基因
21 个基因