Induction of Bad-mediated apoptosis by Sindbis virus infection: Involvement of pro-survival members of the Bcl-2 family
Induction of Bad-mediated apoptosis by Sindbis virus infection: Involvement of pro-survival members of the Bcl-2 family
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DOI：
10.1006/viro.2001.1206
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发表时间：
2002-01-20
期刊：
影响因子：
3.7
通讯作者：
Matsuura, Y
中科院分区：
文献类型：
--
作者：
Moriishi, K;Koura, M;Matsuura, Y
已知Sindbis病毒（SNV）感染可诱导细胞凋亡，而Bcl-2家族的两个促生存成员Bcl-2和Bcl-xL可抑制细胞凋亡。然而，Bcl-2家族的其他成员参与snv诱导的细胞凋亡的机制尚不清楚。在本研究中，我们报道了Bad蛋白（促凋亡Bcl-2家族成员之一）介导SNV感染的哺乳动物细胞的凋亡。Bad蛋白的表达可促进SNV诱导的人胚胎肾293T和幼鼠肾细胞的凋亡。SNV感染也诱导内源性Bad易位进入线粒体，并与Bcl-xL异源二聚化。另一方面，结构上最相似的促生存成员Bcl-2、Bcl-xL和Bcl-w在没有Bad的情况下抑制snv诱导的细胞凋亡，而Mcl-1和A1则没有。Bcl-w能抑制Bad存在时snv诱导的细胞凋亡，而Bcl-xL则不能。Bad可与Bcl-xL或Bcl-2共免疫沉淀，但不能与Bcl-w共免疫沉淀。两种病毒Bcl-2同源物E1B19K和BHRF1也能抑制snv诱导的细胞凋亡，而不考虑Bad的存在，并且与Bad没有物理关联。这些结果表明Bad与Bcl-2家族的促生存成员的直接相互作用有助于snv诱导的细胞凋亡的进展，而非结合成员抑制snv诱导的细胞凋亡，而与Bad的表达无关。(C) 2002 Elsevier Science。
It is known that infection with Sindbis virus (SNV) induces apoptosis, which is inhibited by two pro-survival members of the Bcl-2 family, Bcl-2 and Bcl-xL. However, the mechanism of involvement of the other members of the Bcl-2 family in SNV-induced apoptosis remains unclear. In this study we report that Bad protein, one of the pro-apoptotic Bcl-2 family members, mediates apoptosis in the mammalian cells infected with SNV Expression of Bad was shown to promote SNV-induced apoptosis in human embryonic kidney 293T and baby hamster kidney cells. SNV infection also induced translocation of endogenous Bad into mitochondria and heterodimerization of Bad with Bcl-xL. On the other hand, the structurally most similar pro-survival members, Bcl-2, Bcl-xL, and Bcl-w, suppressed SNV-induced apoptosis in the absence of Bad, whereas Mcl-1 and A1 did not. Bcl-w could inhibit SNV-induced apoptosis in the presence of Bad, but Bcl-xL could not. Bad could be coimmunoprecipitated with Bcl-xL or Bcl-2, but not with Bcl-w. Two viral Bcl-2 homologs, E1B19K and BHRF1, also suppressed SNV-induced apoptosis irrespective of the presence of Bad and no physical association with Bad was observed. These results suggest that direct interaction of Bad with pro-survival members of the Bcl-2 family contributes to the progress of SNV-induced apoptosis and that nonbinding members restrain SNV-induced apoptosis irrespective of Bad expression. (C) 2002 Elsevier Science.