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PMID: 12773388 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

HBXIP functions as a cofactor of survivin in apoptosis suppression.

The EMBO journal ·Vol. 22 ·No. 11 ·2003-06-02 ·Pages 2729-40

Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I, Reed JC

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Apoptosis/physiology Apoptotic Protease-Activating Factor 1 Base Sequence Carcinoma, Hepatocellular/etiology Carrier Proteins/physiology Caspase 9 Caspases/metabolism DNA, Complementary/genetics Enzyme Activation HeLa Cells Hepatitis B/complications,physiopathology Hepatitis B virus/pathogenicity,physiology Humans In Vitro Techniques Inhibitor of Apoptosis Proteins Liver Neoplasms/etiology Microtubule-Associated Proteins/physiology Neoplasm Proteins Phosphorylation Protein Binding Proteins/metabolism RNA, Small Interfering/genetics Recombinant Fusion Proteins/metabolism Survivin Trans-Activators/physiology Viral Nonstructural Proteins/physiology Viral Regulatory and Accessory Proteins
Chemicals
APAF1 protein, human Adaptor Proteins, Signal Transducing Apoptotic Protease-Activating Factor 1 BIRC5 protein, human Carrier Proteins DNA, Complementary Inhibitor of Apoptosis Proteins LAMTOR5 protein, human Microtubule-Associated Proteins Neoplasm Proteins Proteins RNA, Small Interfering Recombinant Fusion Proteins Survivin Trans-Activators Viral Nonstructural Proteins Viral Regulatory and Accessory Proteins hepatitis B virus X protein CASP9 protein, human Caspase 9 Caspases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Marusawa Hiroyuki
The Burnham Institute, La Jolla, CA 92037, USA.
Matsuzawa Shu-Ichi
Welsh Kate
Zou Hua
Armstrong Robert
Tamm Ingo
Reed John C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg263
Published
2003-06-02
Pages
2729-40
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156760
Subset
IM
Grants
NIA NIH HHS · R01 AG015393 · United States
NIA NIH HHS · AG15393-05 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdg263 PMC Full Text View journal details
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