Killar L, White J, Black R, Peschon J
Oncology/Immunoinflammatory Diseases, Wyeth-Ayerst Research, Princeton, New Jersey 08543, USA.
Ann N Y Acad Sci. 1999 Jun 30;878:442-52. doi: 10.1111/j.1749-6632.1999.tb07701.x.
The adamalysins are a family of proteins in the metzincin superfamily of metalloproteases, which also includes the matrix metalloproteinases. There are two subfamilies of adamalysins: the snake venom metalloproteases (SVMPs) and the ADAMs (proteins containing a disintegrin and metalloprotease domain). At least 23 ADAMs have been identified to date. The ADAMs are expressed by a wide variety of cell types, and are involved in functions as diverse as sperm-egg binding, myotube formation, neurogenesis, and proteolytic processing of cell surface proteins. An overview of the ADAM family and their functions will be presented. TACE is a unique member of the ADAM family that cleaves membrane-bound TNF-alpha to generate soluble TNF-alpha. Mice lacking proteolytically active TACE have been generated and characterized. The TACE knock-out results in perinatal lethality. Cells from the TACE-deficient mice release 80-90% less soluble TNF-alpha than do wild-type cells. Irradiated mice that are reconstituted with TACE knock-out hematopoeitic stem cells have markedly reduced levels of serum TNF-alpha following LPS challenge, compared to irradiated mice reconstituted with wild-type cells, suggesting that TACE is the major TNF-alpha converting enzyme in vivo. TACE-deficient cells are compromised in the generation of other soluble proteins that are produced as the result of cleavage of a membrane precursor form, suggesting that TACE is involved in multiple shedding events.
解整合素金属蛋白酶是金属蛋白酶中M12B超家族的一类蛋白质，该超家族还包括基质金属蛋白酶。解整合素金属蛋白酶有两个亚家族：蛇毒金属蛋白酶（SVMPs）和ADAMs（含解整合素和金属蛋白酶结构域的蛋白质）。迄今为止已鉴定出至少23种ADAMs。ADAMs由多种细胞类型表达，并参与多种功能，如精卵结合、肌管形成、神经发生以及细胞表面蛋白的蛋白水解加工。本文将概述ADAM家族及其功能。肿瘤坏死因子α转换酶（TACE）是ADAM家族的一个独特成员，它可切割膜结合型肿瘤坏死因子α（TNF-α）以产生可溶性TNF-α。缺乏蛋白水解活性TACE的小鼠已被培育并进行了特征分析。TACE基因敲除导致围产期致死。与野生型细胞相比，来自TACE缺陷小鼠的细胞释放的可溶性TNF-α减少80 - 90%。与用野生型细胞重建的辐照小鼠相比，用TACE基因敲除的造血干细胞重建的辐照小鼠在脂多糖攻击后血清TNF-α水平显著降低，这表明TACE是体内主要的TNF-α转换酶。TACE缺陷细胞在由膜前体形式切割产生的其他可溶性蛋白质的生成方面存在缺陷，这表明TACE参与多种脱落事件。
