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Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein.

Identifieur interne : 003815 ( Main/Merge ); précédent : 003814; suivant : 003816

Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein.

Auteurs : Ying-Xim Tan ; Timothy H P. Tan ; Marvin J-R Lee ; Puay-Yoke Tham ; Vithiagaran Gunalan ; Julian Druce ; Chris Birch ; Mike Catton ; Nai Yang Fu ; Victor C. Yu ; Yee-Joo Tan

Source :

RBID : pubmed:17428862

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Abstract

The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell lines. In this study, we show that the overexpression of Bcl-XL, a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-XL and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-XL was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-XL. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-XL are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-XL also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-XL at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.

DOI: 10.1128/JVI.00090-07
PubMed: 17428862

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pubmed:17428862

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<term>Chlorocebus aethiops</term>
<term>Gene Deletion</term>
<term>Humans</term>
<term>Immunoprecipitation</term>
<term>Mitochondria (metabolism)</term>
<term>Molecular Sequence Data</term>
<term>Mutation</term>
<term>Protein Structure, Tertiary</term>
<term>Sequence Homology, Amino Acid</term>
<term>Vero Cells</term>
<term>Viral Matrix Proteins (metabolism)</term>
<term>Viral Matrix Proteins (physiology)</term>
<term>Viral Proteins (metabolism)</term>
<term>Viral Proteins (physiology)</term>
<term>bcl-X Protein (metabolism)</term>
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<term>Animaux</term>
<term>Apoptose</term>
<term>Cellules Vero</term>
<term>Données de séquences moléculaires</term>
<term>Délétion de gène</term>
<term>Humains</term>
<term>Immunoprécipitation</term>
<term>Mitochondries (métabolisme)</term>
<term>Mutation</term>
<term>Protéine bcl-X (métabolisme)</term>
<term>Protéines de la matrice virale (métabolisme)</term>
<term>Protéines de la matrice virale (physiologie)</term>
<term>Protéines virales (métabolisme)</term>
<term>Protéines virales (physiologie)</term>
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<term>Protéine bcl-X</term>
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<term>Humains</term>
<term>Immunoprécipitation</term>
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<div type="abstract" xml:lang="en">The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell lines. In this study, we show that the overexpression of Bcl-XL, a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-XL and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-XL was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-XL. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-XL are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-XL also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-XL at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.</div>
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