Abstract
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 α-secretases ADAM10 and 17 as well as by the β-secretase β-APP cleaving enzyme 1. The remaining membrane-bound fragment is a substrate for regulated intramembrane proteolysis by γ-secretase. Our data suggest that therapeutic approaches targeting these proteases should be carefully analyzed for potential side effects on Klotho-mediated physiological processes.
Original language | English (US) |
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Pages (from-to) | 3221-3224 |
Number of pages | 4 |
Journal | FEBS Letters |
Volume | 583 |
Issue number | 19 |
DOIs | |
State | Published - Oct 6 2009 |
Keywords
- ADAM protease
- Klotho
- β-APP cleaving enzyme
- γ-Secretase
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology