Survivin Associates with VDAC2 and Bcl2-Family Proteins at the Mitochondrial Outer Membrane

Survivin is a cancer-associated inhibitor of apoptosis protein (IAP) that can suppress both extrinsic and intrinsic apoptotic pathways. IAPs typically prevent programmed cell death by binding to caspases, but whether survivin behaves as a canonical IAP or can protect cells from death by alternative means has not been fully investigated. Here, we report a novel interaction between survivin and the mitochondrial outer membrane protein, VDAC2, which we show is an indirect association potentially mediated by Bcl2-family members. This novel finding suggests survivin can suppress mitochondrial-mediated apoptosis upstream of caspases and could open a new avenue for targeting survivin in anti-cancer therapy regimes.