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

L Bloch, O Sineshchekova, D Reichenbach, K Reiss… - FEBS letters, 2009 - Elsevier
L Bloch, O Sineshchekova, D Reichenbach, K Reiss, P Saftig, M Kuro-o, C Kaether
FEBS letters, 2009Elsevier
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 …
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.
Elsevier