HBXIP functions as a cofactor of survivin in apoptosis suppression

Survivin is an anti-apoptotic protein that is overexpressed in most human cancers. We show that Survivin forms complexes with a cellular protein, hepatitis B X-interacting protein (HBXIP), which was originally recognized for its association with the X protein of hepatitis B virus (HBX). Survivin-HBXIP complexes, but neither Survivin nor HBXIP individually, bind pro-caspase-9, preventing its recruitment to Apaf1, and thereby selectively suppressing Apoptosis initiated via the mitochondria/cytochrome c pathway. Viral HBX protein also interacts with the survivin- HBXIP complex and suppresses Caspase activation in a survivin-dependent manner. Thus, HBXIP functions as a cofactor for Survivin, and serves as a link between the cellular Apoptosis machinery and a viral pathogen involved in hepatocellular carcinogenesis.