Moss Marcia L, Lambert Millard H
Cognosci Inc., 2 Davis Drive, P.O. Box 12076, Research Triangle Park, NC 27709, USA.
Essays Biochem. 2002;38:141-53. doi: 10.1042/bse0380141.
Many membrane-bound proteins undergo proteolytic release from the membrane, a process known as 'shedding'. Some of the processing events are carried out by enzymes of the ADAM (a disintegrin and metalloproteinase) family, which are also membrane bound. One of the most well known ADAM family members is TACE (tumour necrosis factor-alpha-converting enzyme. TACE was the first ADAM family member to have a known physiological substrate, namely, precursor tumour necrosis factor-alpha. Inhibitors of TACE block the release of the soluble form of this inflammatory cytokine, and are currently being studied in drug discovery projects for the treatment of arthritis. Since the discovery of TACE, physiological substrates for other ADAMs have been determined. This review focuses on the shedding events carried out by TACE and other ADAM family proteinases.
许多膜结合蛋白会经历从膜上的蛋白水解释放过程，这一过程被称为“脱落”。其中一些加工事件是由ADAM（一种解整合素和金属蛋白酶）家族的酶来完成的，这些酶同样也是膜结合的。ADAM家族最著名的成员之一是TACE（肿瘤坏死因子-α转化酶）。TACE是第一个有已知生理底物的ADAM家族成员，即肿瘤坏死因子-α前体。TACE抑制剂可阻断这种炎性细胞因子可溶性形式的释放，目前正在药物研发项目中进行研究，用于治疗关节炎。自TACE被发现以来，其他ADAM的生理底物也已确定。本综述重点关注TACE和其他ADAM家族蛋白酶所引发的脱落事件。
