Intracellular maturation and localization of the tumour necrosis factor α convertase (TACE)
Intracellular maturation and localization of the tumour necrosis factor α convertase (TACE)
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DOI：
10.1042/0264-6021:3470131
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发表时间：
2000-04-01
影响因子：
4.1
通讯作者：
Blobel, CP
中科院分区：
文献类型：
--
作者：
Schlöndorff, J;Becherer, JD;Blobel, CP
肿瘤坏死因子α转换酶(TACE)是一种金属蛋白酶/去整合素，参与了几种蛋白质的胞外结构域脱落，这一过程被认为在炎症、类风湿性关节炎和小鼠的发育中起重要作用。本研究描述了内源性TACE的细胞内成熟和亚细胞定位的特征。与其他蛋白水解性金属蛋白水解酶/去整合素类似，在细胞中发现了两种形式的TACE：全长前体和不含前结构域的成熟形式。原结构域的去除发生在高尔基体的晚期，这与呋喃类原蛋白转换酶在这一过程中的作用一致。当细胞裂解物在EDTA存在下制备时，另一种形式的TACE被检测到，该形式缺乏PRO和细胞质结构域，而不是以羟甲酸基金属蛋白酶抑制剂或1，10-菲咯啉为基础的金属蛋白酶抑制剂。这种形式似乎是由成熟的TACE裂解自己的细胞质尾巴而产生的，这可能解释了为什么在以前的研究中很少发现成熟的TACE。在细胞表面标记实验中，在细胞表面检测到成熟的TACE，但免疫荧光数据表明，TACE主要定位于核周间隙，类似于肿瘤坏死因子(TNF)α的描述。这增加了TACE介导的胞外区脱落除了发生在细胞表面之外，还可能发生在细胞内的可能性。
Tumour necrosis factor alpha convertase (TACE) is a metallo-protease/disintegrin involved in the ectodomain shedding of several proteins, a process thought to be important in inflammation, rheumatoid arthritis and murine development. The characterization of the intracellular maturation and subcellular localization of endogenous TACE is decribed in the present study. Similarly to other proteolytically active metalloprotease/ disintegrins, two forms of TACE are found in cells; a full-length precursor and a mature form lacking the prodomain. Prodomain removal occurs in a late Golgi compartment, consistent with the proposed role of a furin type proprotein convertase in this process. An additional form of TACE, lacking the pro and cytoplasmic domains, is detected when cell lysates are prepared in the presence of EDTA instead of a hydroxamate-based metalloprotease inhibitor or 1,10-phenanthroline. This form appears to be generated by mature TACE cleaving its own cytoplasmic tail and may explain why little mature TACE has been detected in previous studies. In cell-surface labelling experiments, mature TACE was detected on the cell surface but immunofluorescence data indicate that TACE is predominantly localized to a perinuclear compartment similar to that described for tumour necrosis factor (TNF)alpha. This raises the possibility that TACE-mediated ectodomain shedding may occur in an intracellular compartment in addition to the cell surface.