Moss M L., White J M., Lambert M H., Andrews R C.
Cognosci, 2 Davis Drive, PO Box 12076, 27709, Research Triangle Park, NC, USA
Drug Discov Today. 2001 Apr 1;6(8):417-426. doi: 10.1016/s1359-6446(01)01738-x.
Tumor necrosis factor (TNF)-converting enzyme (TACE) and other ADAM proteases (those that contain a disintegrin and a metalloprotease domain) have emerged as potential therapeutic targets in the areas of arthritis, cancer, diabetes and HIV cachexia. TACE is the first ADAM protease to process the known physiological substrate and inflammatory cytokine, membrane-bound precursor-TNF-alpha, to its mature soluble form. Subsequently, TACE was shown to be required for several different processing events such as tumor growth factor-alpha (TGF-alpha) precursor and amyloid precursor protein (APP) cleavage. With the recent discoveries of the proteolytic specificities of other ADAM family members, the information surrounding these metalloproteases is expanding at an exponential rate. This review focuses on TACE and other family members with known proteolytic function as well as the inhibitors of this class of enzyme.
肿瘤坏死因子（TNF）转换酶（TACE）及其他ADAM蛋白酶（即那些含有解整合素和金属蛋白酶结构域的蛋白酶）已成为关节炎、癌症、糖尿病和HIV恶病质领域潜在的治疗靶点。TACE是首个能将已知生理底物及炎性细胞因子——膜结合型前体TNF-α加工成其成熟可溶性形式的ADAM蛋白酶。随后，研究表明TACE参与了多种不同的加工过程，如肿瘤生长因子-α（TGF-α）前体和淀粉样前体蛋白（APP）的裂解。随着最近对其他ADAM家族成员蛋白水解特异性的发现，围绕这些金属蛋白酶的信息正呈指数级增长。本综述重点关注TACE及其他具有已知蛋白水解功能的家族成员，以及这类酶的抑制剂。
