Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein.
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.
Tan
Ying-Xim
YX
Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Tan
Timothy H P
TH
Lee
Marvin J-R
MJ
Tham
Puay-Yoke
PY
Gunalan
Vithiagaran
V
Druce
Julian
J
Birch
Chris
C
Catton
Mike
M
Fu
Nai Yang
NY
Yu
Victor C
VC
Tan
Yee-Joo
YJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology*; D051020:bcl-X Protein / Q000378:metabolism*
D014763:Viral Matrix Proteins; D014764:Viral Proteins; D051020:bcl-X Protein; C488151:sars7a protein, SARS virus