| First Author | Linggi MS | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 14 | Pages | 13801-8 |
| PubMed ID | 15668238 | Mgi Jnum | J:98749 |
| Mgi Id | MGI:3579762 | Doi | 10.1074/jbc.M410435200 |
| Citation | Linggi MS, et al. (2005) Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. J Biol Chem 280(14):13801-8 |
| abstractText | Activation of the p75 neurotrophin receptor leads to a variety of effects within the nervous system, including neuronal apoptosis. Both c-Jun N-terminal kinase (JNK) and the tumor suppressor p53 have been reported to be critical for this receptor to induce cell death; however, the mechanisms by which p75 activates these pathways is undetermined. Here we report that the neurotrophin receptor interacting factor (NRIF) is necessary for p75-dependent JNK activation and apoptosis. Upon nerve growth factor withdrawal, nrif-/- sympathetic neurons underwent apoptosis, whereas p75-mediated death was completely abrogated. The lack of cell death correlated with a lack of JNK activation in the nrif-/- neurons, suggesting that NRIF is a selective mediator for p75-dependent JNK activation and apoptosis. Moreover, we document that NRIF expression is sufficient to induce cell death through a mechanism that requires p53. Taken together, these results establish NRIF as an essential component of the p75 apoptotic pathway. |
