Klotho is a substrate for α-, β- and γ-secretase

被引：205

作者：

Bloch, Laura ^{[1
]}

Sineshchekova, Olga ^{[3
]}

Reichenbach, Daniela ^{[1
]}

Reiss, Karina ^{[2
]}

Saftig, Paul ^{[2
]}

Kuro-o, Makoto ^{[3
]}

Kaether, Christoph ^{[1
]}

机构：

[1] Fritz Lipmann Inst, Leibniz Inst Altersforsch, D-07745 Jena, Germany

[2] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany

[3] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

来源：

FEBS LETTERS | 2009年 / 583卷 / 19期

关键词：

Klotho; gamma-Secretase; ADAM protease; beta-APP cleaving enzyme; INTRAMEMBRANE PROTEOLYSIS; OXIDATIVE STRESS; HORMONE KLOTHO; MEMBRANE; CLEAVAGE; RELEASE; BIOLOGY; PROTEIN; ADAM10; DOMAIN;

D O I：

10.1016/j.febslet.2009.09.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Klotho is an anti-aging protein with different functions of the full-length membrane protein and the secreted hormone-like form. Using overexpression and knock-down approaches as well as embryonic fibroblasts of knock-out mice we present evidence that Klotho is shedded by the alpha-secretases ADAM10 and 17 as well as by the beta-secretase beta-APP cleaving enzyme 1. The remaining membrane-bound fragment is a substrate for regulated intramembrane proteolysis by gamma-secretase. Our data suggest that therapeutic approaches targeting these proteases should be carefully analyzed for potential side effects on Klotho-mediated physiological processes. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：3221 / 3224

页数：4

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