TNF-α converting enzyme (TACE) is inhibited by TIMP-3
TNF-α converting enzyme (TACE) is inhibited by TIMP-3
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DOI：
10.1016/s0014-5793(98)01031-x
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发表时间：
1998-09-11
期刊：
影响因子：
3.5
通讯作者：
Murphy, G
中科院分区：
文献类型：
--
作者：
Amour, A;Slocombe, PM;Murphy, G
TNF-α转化酶（TACE; ADAM-17）是一种膜结合的去整合素金属蛋白酶，可将膜相关细胞因子proTNF-α加工成可溶性形式。由于其假定参与炎性疾病，TACE代表了设计作为治疗剂的特定合成抑制剂的重要靶标。为了研究金属蛋白酶组织抑制剂（TIMPs）和金属蛋白酶合成抑制剂对TACE的抑制作用，从NS 0细胞中过量表达小鼠TACE的催化结构域（rTACE）作为可溶性IG融合蛋白。发现rTACE被肽异羟肟酸抑制剂以及TIMP-3很好地抑制，但不被TIMP-1、TIMP-2和TIMP-4抑制。这些结果表明，TIMP-3，不像其他的TIMP，可能是重要的病理事件的调制，其中TNF-α分泌参与。(C)1998年欧洲生物化学学会联合会。
TNF-alpha converting enzyme (TACE; ADAM-17) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to a soluble form. Because of its putative involvement in inflammatory diseases, TACE represents a significant target for the design of specific synthetic inhibitors as therapeutic agents. In order to study its inhibition by tissue inhibitors of metalloproteinases (TIMPs) and synthetic inhibitors of metalloproteinases, the catalytic domain of mouse TACE (rTACE) was overexpressed as a soluble Ig fusion protein from NS0 cells. rTACE was found to be well inhibited by peptide hydroxamate inhibitors as well as by TIMP-3 but not by TIMP-1, -2 and -4. These results suggest that TIMP-3, unlike the other TIMPs, may be important in the modulation of pathological events in which TNF-alpha secretion is involved. (C) 1998 Federation of European Biochemical Societies.