A bit more than two decades ago, the first Diablo game was released to the world. A game about a lone hero tasked with bringing down Diablo, one of the lords of Hell. This month we highlight a namesake to this hellish lord of terror, the protein DIABLO.

DIABLO, also known as DIABLO homolog or SMAC, is a protein encoded by the DIABLO gene. The protein is mostly famous for its proapoptotic effects, where it binds to and antagonizes IAP (inhibitor of apoptosis) proteins and in doing so frees caspases to activate apoptosis (Verhagen et al. 2000). This effect is accomplished by cleaving the protein within the mitochondria to expose the IAP binding domains. The cleaved protein is released into the cytosol where it can build stable complexes with the surrounding IAPs and cause the cell to die.

This proapotopic function has made DIABLO an interesting protein in the research of several different cancer types in which overexpressing DIABLO sensitizes the tumor cells to apoptosis (Zheng et al. 2010). For instance, experiments have been made with small mimetics that mimic the IAP binding domains of DIABLO to target cancer cells with induced cell death (Bai, Smith & Wang 2014). It is possible that such targeted medicines reduce the amount of cytotoxic chemicals needed for cancer treatment in the future (Sun et al. 2012).

Maybe DIABLO isn't so bad to have around after all?

Casper Winsnes