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PMID: 15218035 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

An IAP-IAP complex inhibits apoptosis.

The Journal of biological chemistry ·Vol. 279 ·No. 33 ·2004-08-13 ·Pages 34087-90

Dohi T, Okada K, Xia F, Wilford CE, Samuel T, Welsh K, Marusawa H, Zou H, Armstrong R, Matsuzawa S, Salvesen GS, Reed JC, Altieri DC

Abstract

Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.

MeSH Terms

Animals Apoptosis Baculoviridae/metabolism Caspase 9 Caspases/metabolism Cell Death Cell Line Cell Line, Tumor Cysteine Endopeptidases/metabolism Dose-Response Relationship, Drug Fibroblasts/metabolism Gene Expression Regulation Glutathione Transferase/metabolism Humans Immunoblotting Inhibitor of Apoptosis Proteins Mice Mice, Transgenic Microtubule-Associated Proteins/metabolism Multienzyme Complexes/metabolism Neoplasm Proteins Precipitin Tests Proteasome Endopeptidase Complex Protein Binding Proteins/chemistry,physiology Recombinant Proteins/metabolism Survivin Time Factors Transfection Transgenes Ubiquitin/metabolism X-Linked Inhibitor of Apoptosis Protein

Chemicals

BIRC5 protein, human Inhibitor of Apoptosis Proteins Microtubule-Associated Proteins Multienzyme Complexes Neoplasm Proteins Proteins Recombinant Proteins Survivin Ubiquitin X-Linked Inhibitor of Apoptosis Protein XIAP protein, human Glutathione Transferase CASP9 protein, human Casp9 protein, mouse Caspase 9 Caspases Cysteine Endopeptidases Proteasome Endopeptidase Complex

Authors & Affiliations

13 authors, click to expand affiliations / ORCID

Dohi Takehiko

Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

Okada Kazuya

Xia Fang

Wilford Casey E

Samuel Temesgen

Welsh Kate

Marusawa Hiroyouki

Zou Hua

Armstrong Robert

Matsuzawa Shu-ichi

Salvesen Guy S

Reed John C

Altieri Dario C

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.C400236200

Published

2004-08-13

Epub

2004-00-24

Pages

34087-90

Language

English

Region

United States

NLM ID

2985121R

Subset

Grants

NIA NIH HHS · AG 15393 · United States

NCI NIH HHS · CA 78810 · United States

NCI NIH HHS · CA 90917 · United States

NHLBI NIH HHS · HL 54131 · United States

External Links

PubMed source DOI: 10.1074/jbc.C400236200 View journal details

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An IAP-IAP complex inhibits apoptosis.

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