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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Apoptosis / physiology*
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Apoptotic Protease-Activating Factor 1
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Base Sequence
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Carcinoma, Hepatocellular / etiology
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Carrier Proteins / physiology*
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Caspase 9
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Caspases / metabolism
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DNA, Complementary / genetics
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Enzyme Activation
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HeLa Cells
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Hepatitis B / complications
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Hepatitis B / physiopathology
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Hepatitis B virus / pathogenicity*
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Hepatitis B virus / physiology
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Humans
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In Vitro Techniques
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Inhibitor of Apoptosis Proteins
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Liver Neoplasms / etiology
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Microtubule-Associated Proteins / physiology*
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Neoplasm Proteins
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Phosphorylation
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Protein Binding
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Proteins / metabolism
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RNA, Small Interfering / genetics
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Recombinant Fusion Proteins / metabolism
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Survivin
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Trans-Activators / physiology
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Viral Nonstructural Proteins / physiology*
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Viral Regulatory and Accessory Proteins
Substances
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APAF1 protein, human
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Adaptor Proteins, Signal Transducing
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Apoptotic Protease-Activating Factor 1
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BIRC5 protein, human
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Carrier Proteins
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DNA, Complementary
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Inhibitor of Apoptosis Proteins
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LAMTOR5 protein, human
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Survivin
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Trans-Activators
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Viral Nonstructural Proteins
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Viral Regulatory and Accessory Proteins
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hepatitis B virus X protein
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CASP9 protein, human
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Caspase 9
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Caspases