BBC3 and brain ischemia: As BID is acting upstream of BAX in cell death signaling, these results indicate that other upstream, proapoptotic BH3-domain containing BCL-2 family proteins (“BH3-only proteins”) such as BIM and PUMA may play a more predominant role in BAX activation after cerebral ischemia (Ren et al., 2010; Engel et al., 2011).