3.6 | PSTPIP2 regulates PANoptosis through Caspase-8
Cysteinyl aspartate specific proteinase (Caspase)-8 has long been considered a promoter of apoptosis and part of the mechanism by which cytotoxic drugs kill cancer cells (Jiang, Qi, Li, Wu, Song & Li, 2021). Caspase-8 controls the interactions between apoptosis, necroptosis, and pyroptosis and determines the type of cell death induced by the activation of cell death signaling (Schwarzer, Laurien & Pasparakis, 2020). A previous study reported a significantly higher number of caspase-8 in PSTPIP2 knockout mice than in the control group (Gurung, Burton & Kanneganti, 2016). Thus, to determine whether PSTPIP2 decreases PANoptosis expression by inhibiting caspase-8, we examined the effect of PSTPIP2 on caspase-8 expression. Notably, we observed a significantly lower number of caspase-8 in PSTPIP2 overexpression groups than in the WT controls (Figure 9A–D). To further elucidate the relationship between PSTPIP2 and Caspase-8, we also verified that Caspase-8 expression increases with the inhibition of PSTPIP2 after PSTPIP2 was inhibited (Figure 10A–D).