Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs
Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs
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DOI：
10.1016/s1097-2765(00)80006-4
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发表时间：
1997-12-01
期刊：
影响因子：
16
通讯作者：
Goldstein, JL
中科院分区：
文献类型：
--
作者：
Rawson, RB;Zelenski, NG;Goldstein, JL
我们报道了一个基因S2P的克隆，该基因编码一种假定的金属蛋白酶，这种蛋白酶是在2位点上对甾醇调节元件结合蛋白（SREBPs）的膜内蛋白水解所必需的，SREBPs是一种膜结合转录因子，可以激活调节胆固醇代谢的基因。SREBPs的活性nh2末端结构域通过两个位点的连续切割从膜上释放：位点1，内质网管腔内；人类S2P基因是通过突变的CHO细胞的互补克隆出来的，突变的CHO细胞不能在Site-2切割srebp，并且是胆固醇营养不良。S2P定义了一个包含锌金属蛋白酶特征的HEXXH序列的新多位膜蛋白家族，假定的锌结合残基的突变消除了S2P的活性，S2P编码一种不寻常的金属蛋白酶，可以在跨膜段内切割蛋白质。
We report the cloning of a gene, S2P, that encodes a putative metalloprotease required for intramembrane proteolysis of sterol-regulatory element-binding proteins (SREBPs) at Site-2, SREBPs are membrane-bound transcription factors that activate genes regulating cholesterol metabolism. The active NH2-terminal domains of SREBPs are released from membranes by sequential cleavage at two sites: Site-1, within the lumen of the endoplasmic reticulum; and Site-5, within a transmembrane segment, The human S2P gene was cloned by complementation of mutant CHO cells that cannot cleave SREBPs at Site-2 and are cholesterol auxotrophs. S2P defines a new family of polytopic membrane proteins that contain an HEXXH sequence characteristic of zinc metalloproteases, Mutation of the putative zinc-binding residues abolishes S2P activity, S2P encodes an unusual metalloprotease that cleaves proteins within transmembrane segments.