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. Author manuscript; available in PMC: 2012 Apr 21.
Published in final edited form as: Trends Mol Med. 2011 Jan;17(1):47–55. doi: 10.1016/j.molmed.2010.09.006

Figure 2. Regulatory mechanisms of PD-L1 and B7-H3 expression.

Figure 2

The PD-L1 promoter has binding sites for transcription factors IRF-1 and NF-κB, so IFN-γ-mediated signaling through the JAK/STAT-1/IRF-1 pathway and TLR ligand-mediated signaling through the MEK/ERK/NF-κB pathway can upregulate PD-L1 gene transcription. Signaling through the PI3K/Akt/mTOR pathway, usually inhibited by PTEN, can activate S6K1, which regulates the 5′ UTR of PD-L1. This results in recruitment of PD-L1 transcripts to polysomes and associated PD-L1 translation. By contrast, miR-513, which can be inhibited by IFN-γ signaling, prevents PD-L1 translation by binding to the PD-L1 3′ UTR. B7-H3 expression can also be enhanced by IFN-γ signaling, perhaps through blocking miR-29, which otherwise represses B7-H3 translation. It seems that different types of cells use overlapping yet divergent pathways to regulate the expression of PD-L1 and B7-H3.