First Author | Bloch L | Year | 2009 |
Journal | FEBS Lett | Volume | 583 |
Issue | 19 | Pages | 3221-4 |
PubMed ID | 19737556 | Mgi Jnum | J:153764 |
Mgi Id | MGI:4366207 | Doi | 10.1016/j.febslet.2009.09.009 |
Citation | Bloch L, et al. (2009) Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett 583(19):3221-4 |
abstractText | 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. |