Fig. 7: Working model. | Cell Death & Disease

Fig. 7: Working model.

From: PD-L1 induction via the MEK-JNK-AP1 axis by a neddylation inhibitor promotes cancer-associated immunosuppression

Fig. 7

MLN4924 activates MEK1/2-ERK1/2 and MKK4/7-JNK kinases to induce c-FOS and c-JUN, respectively, leading to AP-1 activation. Activated AP-1 then binds to its cis-element in the PD-L1 enhancer sequence to transactivate PD-L1 expression. Accumulated PD-L1 contributes to cancer-associated immune evasion to counteract anti-cancer activity of MLN4924. This process can be inhibited by the inhibitor of MEK1/2 (trametinib), JNK (SP600125) and anti-PD-L1 antibody.

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