Figure 6.

A model for IL-12 biogenesis. In isolation, IL-12α covalently misfolds, including a prominent homodimeric species. Assembly with IL-12β inhibits misfolding and allows secretion of bioactive IL-12. Disulfide bridge 3 within IL-12α is essential for IL-12β-induced secretion, whereas disulfide bridges 1 and 2 are dispensable. The deletion of any disulfide bridge as well as ERdj5 overexpression leads to a reduced amount of covalently misfolded IL-12α, with a particularly strong effect of disulfide bridges 1 and 2 on misfolding. Misfolded IL-12α is ultimately targeted for ERAD if no IL-12β is present.