| Title | Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl- XL. | | Author(s) | Pearce AF, Lyles DS | | Institution | Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157. | | Source | J Virol 2009 Jul 8. | | Abstract | Vesicular stomatitis virus (VSV) induces apoptosis via the mitochondrial pathway. The mitochondrial pathway is regulated by the Bcl-2 family of proteins which consists of both pro- and anti-apoptotic members. To determine the relative importance of the multidomain proapoptotic Bcl-2 family members, Bak and Bax, HeLa cells were transfected with Bak and/or Bax siRNA and subsequently infected with recombinant wild-type (rwt) VSV. Our results showed that Bak is more important than Bax for the induction of apoptosis in this system. Bak is regulated by two anti-apoptotic Bcl-2 proteins, Mcl-1, which is rapidly turned over, and Bcl-XL, which is relatively stable. Inhibition of host gene expression by the VSV M protein resulted in the degradation of Mcl-1, but not Bcl- XL. However, inactivation of both Mcl-1 and Bcl- XL was required for cells to undergo apoptosis. While inactivation of Mcl-1 was due to inhibition of its expression, inactivation of Bcl-XL indicates a role for one or more BH3-only Bcl-2 family members. VSV-induced apoptosis was inhibited by transfection with siRNA against Bid, a BH3-only protein that is normally activated by cleavage by caspase-8, the initiator caspase associated with the death receptor pathway. Similarly, treatment with an inhibitor of caspase-8 inhibited VSV-induced apoptosis. These results indicate a role for cross-talk from the death receptor pathway in the activation of the mitochondrial pathway by VSV. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19587033 |
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