Figure 7. Proposed model of JNK1/JNK2 isoform-dependent tumor-specific proliferation controlled by baseline IL-17/IL-17R signaling.

Under steady-state conditions, IL-17R-dependent signaling and, to a lesser extent, IL-17R-independent signaling are required for maintaining baseline A20 production, which serves as a critical negative regulator for restraining the activation of both JNK1 and JNK2. When the baseline IL-17R signaling is severely diminished, the basal A20 production is markedly reduced, leading to aberrant activation of JNK1 or JNK2 in a cell type-dependent manner. When JNK1 is present as the dominant isoform, JNK1 induces c-Jun phosphorylation and promotes c-Jun-dependent proliferation; conversely, when JNK2 is present as the dominant isoform, JNK2 degrades c-Jun and suppresses c-Jun-dependent cell proliferation.