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.
Marusawa
Hiroyuki
H
The Burnham Institute, La Jolla, CA 92037, USA.
Matsuzawa
Shu-Ichi
S
Welsh
Kate
K
Zou
Hua
H
Armstrong
Robert
R
Tamm
Ingo
I
Reed
John C
JC
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002352:Carrier Proteins / Q000502:physiology*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D006367:HeLa Cells; D006509:Hepatitis B / Q000150:complications / Q000503:physiopathology; D006515:Hepatitis B virus / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000209:etiology; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D009363:Neoplasm Proteins; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000077022:Survivin; D015534:Trans-Activators / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D053477:Apoptotic Protease-Activating Factor 1; C107489:BIRC5 protein, human; D002352:Carrier Proteins; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; C110719:LAMTOR5 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases