Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease
Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease
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DOI：
10.1111/j.1742-4658.2005.04832.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.4
通讯作者：
Aitken, A
中科院分区：
文献类型：
--
作者：
Mackie, S;Aitken, A
利用酵母双杂交技术，以14-3-3 zeta蛋白为诱饵，从人脑cDNA文库中分离到两个新的14 - 3 -3结合蛋白。其中之一编码神经特异性犰狳重复蛋白的C-末端，δ-连环蛋白（神经斑嗜蛋白相关臂重复蛋白或neurojungin）。来自脑裂解物的δ-连环蛋白保留在14-3-3亲和柱上。人蛋白质中丝氨酸1072的突变和小鼠同源物中等同位点中丝氨酸1094的突变（在14-3-3的共有结合基序中）消除了14-3-3在体外和转染细胞中与δ-连环蛋白的结合。δ-连环蛋白与早老素-1结合，早老素-1由家族性阿尔茨海默病中最常突变的基因编码。另一个克隆被鉴定为53 kDa的胰岛素受体酪氨酸激酶底物蛋白（IRSp 53）。人IRSp 53与参与齿状核红核-苍白球路易氏体萎缩的基因产物相互作用，这是一种与萎缩蛋白-1的谷氨酰胺重复扩增相关的常染色体隐性遗传疾病。
We isolated two novel 14-3-3 binding proteins using 14-3-3 zeta as bait in a yeast two-hybrid screen of a human brain cDNA library. One of these encoded the C-terminus of a neural specific armadillo-repeat protein, delta-catenin (neural plakophilin-related arm-repeat protein or neurojungin). delta-Catenin from brain lysates was retained on a 14-3-3 affinity column. Mutation of serine 1072 in the human protein and serine 1094 in the equivalent site in the mouse homologue (in a consensus binding motif for 14-3-3) abolished 14-3-3 binding to delta-catenin in vitro and in transfected cells. delta-catenin binds to presenilin-1, encoded by the gene most commonly mutated in familial Alzheimer's disease. The other clone was identified as the insulin receptor tyrosine kinase substrate protein of 53 kDa (IRSp53). Human IRSp53 interacts with the gene product implicated in dentatorubral-pallidoluysian atrophy, an autosomal recessive disorder associated with glutamine repeat expansion of atrophin-1.