一种可加工肿瘤坏死因子-α前体的去整合素金属蛋白酶的克隆

Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.

作者信息

Moss M L, Jin S L, Milla M E, Bickett D M, Burkhart W, Carter H L, Chen W J, Clay W C, Didsbury J R, Hassler D, Hoffman C R, Kost T A, Lambert M H, Leesnitzer M A, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton L K, Schoenen F, Seaton T, Su J L, Becherer J D

机构信息

Department of Molecular Biochemistry, Glaxo Wellcome Research and Development Inc., Research Triangle Park, North Carolina 27709, USA.

出版信息

Nature. 1997 Feb 20;385(6618):733-6. doi: 10.1038/385733a0.

DOI:10.1038/385733a0

PMID:9034191

Abstract

Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a variety of inflammatory disease states. The protein exists as a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA. TACE is a membrane-bound disintegrin metalloproteinase. Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development. The expression of recombinant TACE (rTACE) results in the production of functional enzyme that correctly processes precursor TNF-alpha to the mature form. The rTACE provides a readily available source of enzyme to help in the search for new anti-inflammatory agents that target the final processing stage of TNF-alpha production.

摘要

肿瘤坏死因子-α（TNF-α）是一种细胞因子，它在多种炎症性疾病状态中发挥作用。该蛋白以相对分子质量为26K的膜结合前体形式存在，可被TNF-α转换酶（TACE）加工，生成分泌型17K成熟TNF-α。我们已经纯化了TACE并克隆了其互补DNA。TACE是一种膜结合的去整合素金属蛋白酶。与其他含去整合素的酶进行结构比较表明，TACE是独特的，与参与髓磷脂降解的酶MADM以及对神经元发育很重要的MADM果蝇同源物KUZ具有显著的序列同一性。重组TACE（rTACE）的表达导致产生功能性酶，该酶可将前体TNF-α正确加工成成熟形式。rTACE提供了一种易于获得的酶源，有助于寻找针对TNF-α产生最终加工阶段的新型抗炎剂。