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Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-X L Protein

2007; American Society for Microbiology; Volume: 81; Issue: 12 Linguagem: Inglês

10.1128/jvi.00090-07

1098-5514

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,

Animal Virus Infections Studies

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