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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 : 003D18 ( Main/Merge ); précédent : 003D17; suivant : 003D19

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 [Singapour] ; Timothy H. P. Tan [Singapour] ; Marvin J.-R. Lee [Singapour] ; Puay-Yoke Tham [Singapour] ; Vithiagaran Gunalan [Singapour] ; Julian Druce [Australie] ; Chris Birch [Australie] ; Mike Catton [Australie] ; NAI YANG FU [Singapour] ; Victor C. Yu [Singapour] ; Yee-Joo Tan [Singapour]

Source :

RBID : Pascal:07-0315403

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English descriptors

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 Al) 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.

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Pascal:07-0315403

Le document en format XML

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<term>Coronavirus</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-X
<sub>L</sub>
, 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-X
<sub>L</sub>
and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and Al) 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-X
<sub>L</sub>
was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-X
<sub>L</sub>
. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-X
<sub>L</sub>
are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-X
<sub>L</sub>
also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-X
<sub>L</sub>
at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.</div>
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