Fig. 1

Mechanisms of epigenetic, post-transcriptional, and post-translational modifications of PD-L1. The mechanisms of epigenetic and post-transcriptional modification of PD-L1 include histone deacetylation of the PD-L1 promoter region by HDACs and regulation by microRNAs (miRNAs), such as miR-34a, miR-200, miR-513, and miR-570. Both of these mechanisms result in downregulation of PD-L1. There are several mechanisms of post-translational modification in PD-L1 protein: GSK3β induces phosphorylation-dependent proteasome degradation of PD-L1, leading to downregulation of PD-L1; EGF-mediated glycosylation inactivates GSK3β, which stabilizes PD-L1; CSN5-mediated deubiquitination induced by TNF-α, which leads to stabilization of PD-L1