| First Author | Sainski AM | Year | 2014 |
| Journal | J Cell Biol | Volume | 206 |
| Issue | 7 | Pages | 867-76 |
| PubMed ID | 25246614 | Mgi Jnum | J:216976 |
| Mgi Id | MGI:5610097 | Doi | 10.1083/jcb.201405051 |
| Citation | Sainski AM, et al. (2014) Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation. J Cell Biol 206(7):867-76 |
| abstractText | Previous studies have shown that human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. Herein, we show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell death. Levels of active Bak are higher in HIV-infected T cells that express Casp8p41. Conversely, targeted mutations in the Bak-interacting domain diminish Bak binding and Casp8p41-mediated cell death. Similar mutations in procaspase 8 impair the ability of HIV to kill infected T cells. These observations support a novel paradigm in which HIV converts a normal cellular constituent into a direct activator that functions like a BH3-only protein. |
