| First Author | Kundu M | Year | 2009 |
| Journal | Nat Immunol | Volume | 10 |
| Issue | 8 | Pages | 918-26 |
| PubMed ID | 19597496 | Mgi Jnum | J:151578 |
| Mgi Id | MGI:4354459 | Doi | 10.1038/ni.1754 |
| Citation | Kundu M, et al. (2009) A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis. Nat Immunol 10(8):918-26 |
| abstractText | Apoptosis is central to the interaction between pathogenic mycobacteria and host macrophages. Caspase-8-dependent apoptosis of infected macrophages, which requires activation of the mitogen-activated protein (MAP) kinase p38, lowers the spread of mycobacteria. Here we establish a link between the release of tumor necrosis factor (TNF) and mycobacteria-mediated macrophage apoptosis. TNF activated a pathway involving the kinases ASK1, p38 and c-Abl. This pathway led to phosphorylation of FLIP(S), which facilitated its interaction with the E3 ubiquitin ligase c-Cbl. This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. Our findings identify a previously unappreciated signaling pathway needed for Mycobacterium tuberculosis-triggered macrophage cell death. |
