HBXIP Functions As a Cofactor of Survivin in Apoptosis Suppression

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 May 30

PMID 12773388

Citations 167

Authors

Hiroyuki Marusawa

Shu-Ichi Matsuzawa

Kate Welsh

Hua Zou

Robert Armstrong

Ingo Tamm

John C Reed

Affiliations

Soon will be listed here.

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.

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References

Salvesen G . Caspases: opening the boxes and interpreting the arrows. Cell Death Differ. 2002; 9(1):3-5. DOI: 10.1038/sj.cdd.4400963. View

Grossman D, Kim P, Brash D, Tognin S, Marchisio P, Altieri D . Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53. J Clin Invest. 2001; 108(7):991-9. PMC: 200956. DOI: 10.1172/JCI13345. View

Yang J, Liu X, Bhalla K, Kim C, Ibrado A, Cai J . Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997; 275(5303):1129-32. DOI: 10.1126/science.275.5303.1129. View

Zhou Q, Snipas S, Orth K, Muzio M, Dixit V, Salvesen G . Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J Biol Chem. 1997; 272(12):7797-800. DOI: 10.1074/jbc.272.12.7797. View

Deveraux Q, Takahashi R, Salvesen G, Reed J . X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 1997; 388(6639):300-4. DOI: 10.1038/40901. View

Ambrosini G, Adida C, Altieri D . A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997; 3(8):917-21. DOI: 10.1038/nm0897-917. View

Li P, Nijhawan D, Budihardjo I, Srinivasula S, Ahmad M, Alnemri E . Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91(4):479-89. DOI: 10.1016/s0092-8674(00)80434-1. View

Melegari M, Scaglioni P, Wands J . Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication. J Virol. 1998; 72(3):1737-43. PMC: 109461. DOI: 10.1128/JVI.72.3.1737-1743.1998. View

Cryns V, Yuan J . Proteases to die for. Genes Dev. 1998; 12(11):1551-70. DOI: 10.1101/gad.12.11.1551. View

10.

Gottlob K, Fulco M, Levrero M, Graessmann A . The hepatitis B virus HBx protein inhibits caspase 3 activity. J Biol Chem. 1998; 273(50):33347-53. DOI: 10.1074/jbc.273.50.33347. View

11.

Tamm I, Wang Y, Sausville E, Scudiero D, Vigna N, Oltersdorf T . IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 1998; 58(23):5315-20. View

12.

Li F, Ambrosini G, Chu E, Plescia J, Tognin S, Marchisio P . Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998; 396(6711):580-4. DOI: 10.1038/25141. View

13.

Deveraux Q, Reed J . IAP family proteins--suppressors of apoptosis. Genes Dev. 1999; 13(3):239-52. DOI: 10.1101/gad.13.3.239. View

14.

Stennicke H, Deveraux Q, Humke E, Reed J, Dixit V, Salvesen G . Caspase-9 can be activated without proteolytic processing. J Biol Chem. 1999; 274(13):8359-62. DOI: 10.1074/jbc.274.13.8359. View

15.

Zou H, Li Y, Liu X, Wang X . An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem. 1999; 274(17):11549-56. DOI: 10.1074/jbc.274.17.11549. View

16.

Murakami S . Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol. 2001; 36(10):651-60. DOI: 10.1007/s005350170027. View

17.

Velculescu V, Madden S, Zhang L, Lash A, Yu J, Rago C . Analysis of human transcriptomes. Nat Genet. 1999; 23(4):387-8. DOI: 10.1038/70487. View

18.

Marusawa H, Uemoto S, Hijikata M, Ueda Y, Tanaka K, Shimotohno K . Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen. Hepatology. 2000; 31(2):488-95. DOI: 10.1002/hep.510310232. View

19.

Lok A . Hepatitis B infection: pathogenesis and management. J Hepatol. 2000; 32(1 Suppl):89-97. DOI: 10.1016/s0168-8278(00)80418-3. View

20.

Verdecia M, Huang H, Dutil E, Kaiser D, Hunter T, Noel J . Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Biol. 2000; 7(7):602-8. DOI: 10.1038/76838. View