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The zinc finger protein NRIF interacts with the neurotrophin receptor p75 NTR and participates in programmed cell death
Author(s) -
Casademunt Elisabeth,
Carter Bruce D.,
Benzel Isabel,
Frade José M.,
Dechant Georg,
Barde YvesAlain
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.21.6050
Subject(s) - biology , krüppel , low affinity nerve growth factor receptor , zinc finger , programmed cell death , microbiology and biotechnology , neurotrophin , embryonic stem cell , receptor , nerve growth factor , gene , genetics , transcription factor , apoptosis
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.