The zinc finger protein NRIF interacts with the neurotrophin receptor p75NTR and participates in programmed cell death
The zinc finger protein NRIF interacts with the neurotrophin receptor p75NTR and participates in programmed cell death
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DOI：
10.1093/emboj/18.21.6050
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发表时间：
1999-11-01
期刊：
影响因子：
11.4
通讯作者：
Barde, YA
中科院分区：
文献类型：
--
作者：
Casademunt, E;Carter, BD;Barde, YA
NRIF（神经营养因子受体相互作用因子）是Kruppel家族中普遍表达的锌指蛋白，与神经营养因子受体p75（NTR）相互作用。首先在酵母中检测到这种相互作用，然后利用重组GST-NRIF融合物和真核细胞表达的p75（NTR）进行生化证实。携带编码NRIF p75（NTR）结合域外显子缺失的转基因小鼠显示出强烈依赖于遗传背景的表型。而在F-2代，只有有限的（20%）胚胎致死率，在同源BL6菌株中，nrif（-/-）小鼠不能存活超过E12，但在Sv129背景下存活并健康到成年。在小鼠胚胎神经视网膜中检测了NRIF参与p75(NTR)/ ngf介导的发育性细胞死亡。nrif基因的破坏导致细胞死亡的减少，这在数量上与p75（NTR-/-）和ngf（-/-）小鼠中观察到的情况没有区别。这些结果表明，NRIF是细胞内p75（NTR）结合蛋白，在发育过程中传导细胞死亡信号。
NRIF (neurotrophin receptor interacting factor) is a ubiquitously expressed zinc finger protein of the Kruppel 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.