| First Author | Shen HM | Year | 2004 |
| Journal | Mol Cell Biol | Volume | 24 |
| Issue | 13 | Pages | 5914-22 |
| PubMed ID | 15199146 | Mgi Jnum | J:91603 |
| Mgi Id | MGI:3047519 | Doi | 10.1128/MCB.24.13.5914-5922.2004 |
| Citation | Shen HM, et al. (2004) Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Mol Cell Biol 24(13):5914-22 |
| abstractText | Oxidative stress and reactive oxygen species (ROS) can elicit and modulate various physiological and pathological processes, including cell death. However, the mechanisms controlling ROS-induced cell death are largely unknown. Data from this study suggest that receptor-interacting protein (RIP) and tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2), two key effector molecules of TNF signaling, are essential for ROS-induced cell death. We found that RIP(-/-) or TRAF2(-/-) mouse embryonic fibroblasts (MEF) are resistant to ROS-induced cell death when compared to wild-type cells, and reconstitution of RIP and TRAF2 gene expression in their respective deficient MEF cells restored their sensitivity to H(2)O(2)-induced cell death. We also found that RIP and TRAF2 form a complex upon H(2)O(2) exposure, but without the participation of TNFR1. The colocalization of RIP with a membrane lipid raft marker revealed a possible role of lipid rafts in the transduction of cell death signal initiated by H(2)O(2). Finally, our results demonstrate that activation of c-Jun NH(2)-terminal kinase 1 is a critical event downstream of RIP and TRAF2 in mediating ROS-induced cell death. Therefore, our study uncovers a novel signaling pathway regulating oxidative stress-induced cell death. |
