Black Roy A, Doedens John R, Mahimkar Rajeev, Johnson Richard, Guo Lin, Wallace Alison, Virca Duke, Eisenman June, Slack Jennifer, Castner Beverly, Sunnarborg Susan W, Lee David C, Cowling Rebecca, Jin Guixian, Charrier Keith, Peschon Jacques J, Paxton Ray
Amgen Inc., 51 University Street, Seattle, WA 98101, USA.
Biochem Soc Symp. 2003(70):39-52. doi: 10.1042/bss0700039.
Tumour necrosis factor alpha (TNF alpha)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor alpha, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.
肿瘤坏死因子α（TNFα）转换酶（TACE/ADAM-17，其中ADAM代表去整合素和金属蛋白酶）从细胞表面释放TNF及其他几种蛋白质的细胞外结构域。先前的研究发现，虽然纯化的TACE优先切割代表TNF和转化生长因子α中加工位点的肽段，但细胞内的这种酶仍然能够非常有效地切割具有不同切割位点的蛋白质。最近的研究工作，确定了p75 TNF受体中的切割位点，量化了其他肽段被TACE切割的敏感性，并鉴定了其他蛋白质底物，突显了TACE与底物相互作用的复杂性。除了底物特异性外，激活细胞的因子导致脱落速率增加的潜在机制仍知之甚少。该领域最近的研究工作，利用肽底物作为细胞TACE活性的探针，表明该酶的内在活性以某种方式增加了。
