Format

Send to

Choose Destination
FEBS Lett. 2009 Oct 6;583(19):3221-4. doi: 10.1016/j.febslet.2009.09.009. Epub 2009 Sep 6.

Klotho is a substrate for alpha-, beta- and gamma-secretase.

Author information

1
Leibniz Institut für Altersforschung-Fritz Lipmann Institut, Beutenbergstr. 11, 07745 Jena, Germany.

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 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.

PMID:
19737556
PMCID:
PMC2757472
DOI:
10.1016/j.febslet.2009.09.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center