In addition to proinflammatory cytokines such as IL-1 and IFN-γ, the signaling via IFIH1 and various other pathogen recognition receptors mediate β-cell apoptotic death: upregulate certain BH3 proteins and also promote the secretion of numerous chemokines. Certain BH3 “sensitizer” proteins, for example, DP5, bind to BCL2 and BCL-XL which inhibit BAX and BAK activation and at the same time liberate the “activator” proteins (such as BIM and PUMA). PTPN2 is a negative regulator of the pancreatic β-cell apoptosis that reduces the BH3 protein-related apoptotic activation cascade in the β-cell.
