POSTTRANSLATIONAL PROCESSING OF THE LDL RECEPTOR AND ITS GENETIC DISRUPTION IN FAMILIAL HYPERCHOLESTEROLEMIA
POSTTRANSLATIONAL PROCESSING OF THE LDL RECEPTOR AND ITS GENETIC DISRUPTION IN FAMILIAL HYPERCHOLESTEROLEMIA
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DOI：
10.1016/0092-8674(82)90276-8
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发表时间：
1982-01-01
期刊：
影响因子：
64.5
通讯作者：
BROWN, MS
中科院分区：
文献类型：
--
作者：
TOLLESHAUG, H;GOLDSTEIN, JL;BROWN, MS
用35S-Me孵育培养的人成纤维细胞，然后用抗低密度脂蛋白受体的单抗进行免疫沉淀，研究低密度脂蛋白受体的合成。该受体被合成为表观相对分子质量为120千道尔顿(Kd)的前体，并被转化为160kd的成熟形式。这种新的加工形式发生在合成后15-30分钟，似乎不是由于N-连接的寡糖链的简单添加。来自一名表型为纯合子家族性高胆固醇血症的儿童的成纤维细胞显示受体处理中断。这个孩子在低密度脂蛋白受体基因上有两个不同的突变等位基因。一个等位基因来自他的杂合子母亲，产生了一个异常的120kd蛋白质，不能加工成成熟的160kd形式。另一个等位基因，遗传自他的杂合子父亲，产生一个受体，作为一个细长的170kd前体合成，经历40kd的MW增加，形成一个异常大的210kd的受体。
Synthesis of the low density lipoprotein (LDL) receptor was studied by incubation of cultured human fibroblasts with 35S-Me followed by immunoprecipitation with a monoclonal antireceptor antibody. The receptor was synthesized as a precursor with an apparent MW of 120 kilodaltons (kd) that was converted to a mature form of 160 kd. This novel form of processing occurred 15-30 min after synthesis and did not appear to be due to the simple addition of N-linked oligosaccharide chains. Fibroblasts from a child with the phenotype of homozygous familial hypercholesterolemia showed a disruption in receptor processing. This child has 2 different mutants alleles at the LDL receptor locus. One allele, inherited from his heterozygous mother, produces an abnormal 120 kd protein that cannot be processed to the mature 160 kd form. The other allele, inherited from his heterozygous father, produces a receptor that is synthesized as an elongated 170 kd precursor which undergoes a 40 kd increase in MW to form an abnormally large receptor of 210 kd.