Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor.

Linggi MS, Burke TL, Williams BB, Harrington A, Kraemer R, Hempstead BL, Yoon SO, Carter BD
J Biol Chem. 2005 280 (14): 13801-8

PMID: 15668238 · DOI:10.1074/jbc.M410435200

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.

MeSH Terms (19)

Adrenergic Fibers Animals Apoptosis Caspases Cells, Cultured DNA-Binding Proteins Enzyme Activation Humans Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases Mice Mice, Knockout Nerve Growth Factor Neurons Rats Receptor, Nerve Growth Factor Receptors, Nerve Growth Factor Signal Transduction Tumor Suppressor Protein p53

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