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  • 标题:Notch receptor cleavage depends on but is not directly executed by presenilins
  • 本地全文:下载
  • 作者:Yoshihito Taniguchi ; Helena Karlström ; Johan Lundkvist
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2002
  • 卷号:99
  • 期号:6
  • 页码:4014-4019
  • DOI:10.1073/pnas.052017699
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Notch receptors undergo three distinct proteolytic cleavages during maturation and activation. The third cleavage occurs within the plasma membrane and results in the release and translocation of the intracellular domain into the nucleus to execute Notch signaling. This so-called {gamma}-secretase cleavage is under the control of presenilins, but it is not known whether presenilins themselves carry out the cleavage or whether they act by means of yet-unidentified {gamma}-secretase(s). In this article, we show that Notch intracellular cleavage in intact cells completely depends on presenilins. In contrast, partial purification of the Notch cleavage activity reveals an activity, which is present only in protein extracts from presenilin-containing cells, and which does not comigrate with presenilin. This finding provides evidence for the existence of a specific Notch-processing activity, which is physically distinct from presenilins. We conclude from these experiments that presenilins are critically required for Notch intracellular cleavage but are not themselves directly mediating the cleavage.
  • 关键词:secretase‖Alzheimer's disease‖neurodegenerative disease‖HES gene
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