HBXIP functions as a cofactor of survivin in apoptosis suppression

Abstract

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.