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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 : 003B60 ( Main/Exploration ); précédent : 003B59; suivant : 003B61

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

Descripteurs français

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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</teiHeader>
<front>
<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>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Singapour</li>
</country>
</list>
<tree>
<country name="Singapour">
<noRegion>
<name sortKey="Tan, Ying Xim" sort="Tan, Ying Xim" uniqKey="Tan Y" first="Ying-Xim" last="Tan">Ying-Xim Tan</name>
</noRegion>
<name sortKey="Gunalan, Vithiagaran" sort="Gunalan, Vithiagaran" uniqKey="Gunalan V" first="Vithiagaran" last="Gunalan">Vithiagaran Gunalan</name>
<name sortKey="Lee, Marvin J R" sort="Lee, Marvin J R" uniqKey="Lee M" first="Marvin J.-R." last="Lee">Marvin J.-R. Lee</name>
<name sortKey="Nai Yang Fu" sort="Nai Yang Fu" uniqKey="Nai Yang Fu" last="Nai Yang Fu">NAI YANG FU</name>
<name sortKey="Tan, Timothy H P" sort="Tan, Timothy H P" uniqKey="Tan T" first="Timothy H. P." last="Tan">Timothy H. P. Tan</name>
<name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name>
<name sortKey="Tham, Puay Yoke" sort="Tham, Puay Yoke" uniqKey="Tham P" first="Puay-Yoke" last="Tham">Puay-Yoke Tham</name>
<name sortKey="Yu, Victor C" sort="Yu, Victor C" uniqKey="Yu V" first="Victor C." last="Yu">Victor C. Yu</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Druce, Julian" sort="Druce, Julian" uniqKey="Druce J" first="Julian" last="Druce">Julian Druce</name>
</noRegion>
<name sortKey="Birch, Chris" sort="Birch, Chris" uniqKey="Birch C" first="Chris" last="Birch">Chris Birch</name>
<name sortKey="Catton, Mike" sort="Catton, Mike" uniqKey="Catton M" first="Mike" last="Catton">Mike Catton</name>
</country>
</tree>
</affiliations>
</record>

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