Mutations at the P1′ position of Notch1 decrease intracellular domain stability rather than cleavage by γ-secretase
Mutations at the P1′ position of Notch1 decrease intracellular domain stability rather than cleavage by γ-secretase
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DOI：
10.1016/s0006-291x(02)02705-5
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发表时间：
2002-12-13
影响因子：
3.1
通讯作者：
Seiffert, D
中科院分区：
文献类型：
--
作者：
Blat, Y;Meredith, JE;Seiffert, D
γ-分泌酶是一种独特的蛋白酶，可在多种底物蛋白的跨膜结构域内进行切割。 γ-分泌酶底物包括Notch受体家族的成员和淀粉样蛋白前体蛋白。在本研究中，我们使用无细胞 Notch 裂解测定和特定的 γ 分泌酶抑制剂来研究 γ 分泌酶对 Notch 的裂解。使用该测定，我们发现，与之前的报道相反，Notch1 P1'位置上缬氨酸的存在对于γ-分泌酶裂解来说不是必需的。我们的结果表明，Notch 胞内结构域裂解产物 N 末端存在缬氨酸对其稳定性很重要。因此，就缺乏序列特异性而言，Notch 切割似乎与 APP 切割非常相似。 (C) 2002 年爱思唯尔科学（美国）。版权所有。
gamma-Secretase is a unique protease which cleaves within the transmembrane domain of several substrate proteins. Among gamma-secretase substrates are members of the Notch family of receptors and the amyloid precursor protein. In this study we used a cell-free Notch-cleavage assay and specific gamma-secretase inhibitors to study the cleavage of Notch by gamma-secretase. Using this assay, we found that, in contrast to previous reports, the presence of valine at the P1' position of Notch1 is not required for gamma-secretase cleavage. Our results suggest that the presence of valine at the N-terminus of the Notch intracellular domain cleavage product is important for its stability. Thus it appears that Notch cleavage is very similar to APP cleavage with respect to the lack of sequence specificity. (C) 2002 Elsevier Science (USA). All rights reserved.