The zinc finger protein NRIF interacts with the neurotrophin receptor p75NTR and participates in programmed cell death

NRIF (neurotrophin receptor interacting factor) is a ubiquitously expressed zinc finger protein of the Krüppel family which interacts with the neurotrophin receptor p75 NTR . The interaction was first detected in yeast and then biochemically confirmed using recombinant GST–NRIF fusions and p75 NTR expressed by eukaryotic cells. Transgenic mice carrying a deletion in the exon encoding the p75 NTR ‐binding domain of NRIF display a phenotype which is strongly dependent upon genetic background. While at the F 2 generation there is only limited (20%) embryonic lethality, in a congenic BL6 strain nrif −/− mice cannot survive beyond E12, but are viable and healthy to adulthood in the Sv129 background. The involvement of NRIF in p75 NTR /NGF‐mediated developmental cell death was examined in the mouse embryonic neural retina. Disruption of the nrif gene leads to a reduction in cell death which is quantitatively indistinguishable from that observed in p75 NTR−/− and ngf −/− mice. These results indicate that NRIF is an intracellular p75 NTR ‐binding protein transducing cell death signals during development.