A γ-secretase-like intramembrane cleavage of TNFα by the GxGD aspartyl protease SPPL2b
A γ-secretase-like intramembrane cleavage of TNFα by the GxGD aspartyl protease SPPL2b
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DOI：
10.1038/ncb1450
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发表时间：
2006-08-01
影响因子：
21.3
通讯作者：
Haass, Christian
中科院分区：
文献类型：
--
作者：
Fluhrer, Regina;Grammer, Gudula;Haass, Christian
分泌酶和信号肽肽酶（SPP）是介导膜内蛋白水解的不常见的GxGD乙酰基蛋白酶。除了SPP之外，还鉴定了一个功能未知的SPP样蛋白（SPPLs）家族。我们证明，SPPL2b利用多个膜内裂解释放肿瘤坏死因子α（TNF α）的细胞内结构域进入胞质溶胶和羧基末端对应物进入细胞外空间。这些研究结果表明，共同的原则，调节膜内蛋白水解的GxGD乙酰蛋白酶。
secretase and signal peptide peptidase ( SPP) are unusual GxGD aspartyl proteases, which mediate intramembrane proteolysis. In addition to SPP, a family of SPP-like proteins ( SPPLs) of unknown function has been identified. We demonstrate that SPPL2b utilizes multiple intramembrane cleavages to liberate the intracellular domain of tumor necrosis factor alpha ( TNF alpha) into the cytosol and the carboxy-terminal counterpart into the extracellular space. These findings suggest common principles for regulated intramembrane proteolysis by GxGD aspartyl proteases.