Fig. 5

Regulatory pathways of PD-L1 through glycosylation. a Sigma1 promotes N-glycosylation in both the ER and Golgi, and FKBP51 s also augment N-glycosylation of PD-L1 in the ER. EGF upregulates B3GNT3, facilitating the glycosylation of PD-L1 in the Golgi apparatus. Conversely, GSK3β inhibits PD-L1 glycosylation. GLT1D1, GFT, and B4GALT1 promote the N-glycosylation of PD-L1. β-catenin induces N-glycosyltransferase STT3 transcription, stabilizing the oligosaccharide chains of PD-L1 in the ER and upregulating PD-L1. PAR2 activates the N-glycosyltransferases STT3A and STT3B, enhancing the glycosylation of PD-L1. TMUB1 enhances the N-glycosylation and stability of PD-L1 by recruiting STT3A. TGF-β1 activates the c-Jun/STT3A signaling pathway, promoting N-glycosylation of PD-L1. At the transcriptional level, FAT4 reduces PD-L1 mRNA expression and downregulates STT3A through β-catenin, resulting in abnormal glycosylation of PD-L1. SEC61G induces PD-L1 translation and N-glycosylation. MCT4 stabilizes PD-L1 by promoting its glycosylation through the classical WNT pathway. Notably, secreted PD-L1 splicing variants exist, with only those possessing N-linked glycosylation sites exhibiting stable secretion. b GALNT2/14 and GFAT1 potentially increase the O-glycosylation of PD-L1. The black arrows denote positive regulation, while the red arrows indicate negative regulation