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

Laura Bloch, Olga Sineshchekova, Daniela Reichenbach, Karina Reiss, Paul Saftig, Makoto Kuro-o, Christoph Kaether

Research output: Contribution to journalArticle

131 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3221-3224
Number of pages4
JournalFEBS Letters
Volume583
Issue number19
DOIs
StatePublished - Oct 6 2009

Fingerprint

Amyloid Precursor Protein Secretases
Substrates
Proteolysis
Physiological Phenomena
Fibroblasts
Knockout Mice
Membrane Proteins
Peptide Hydrolases
Aging of materials
Hormones
Membranes
Enzymes
Proteins
Therapeutics

Keywords

  • β-APP cleaving enzyme
  • γ-Secretase
  • ADAM protease
  • Klotho

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Bloch, L., Sineshchekova, O., Reichenbach, D., Reiss, K., Saftig, P., Kuro-o, M., & Kaether, C. (2009). Klotho is a substrate for α-, β- and γ-secretase. FEBS Letters, 583(19), 3221-3224. https://doi.org/10.1016/j.febslet.2009.09.009

Klotho is a substrate for α-, β- and γ-secretase. / Bloch, Laura; Sineshchekova, Olga; Reichenbach, Daniela; Reiss, Karina; Saftig, Paul; Kuro-o, Makoto; Kaether, Christoph.

In: FEBS Letters, Vol. 583, No. 19, 06.10.2009, p. 3221-3224.

Research output: Contribution to journalArticle

Bloch, L, Sineshchekova, O, Reichenbach, D, Reiss, K, Saftig, P, Kuro-o, M & Kaether, C 2009, 'Klotho is a substrate for α-, β- and γ-secretase', FEBS Letters, vol. 583, no. 19, pp. 3221-3224. https://doi.org/10.1016/j.febslet.2009.09.009
Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-o M et al. Klotho is a substrate for α-, β- and γ-secretase. FEBS Letters. 2009 Oct 6;583(19):3221-3224. https://doi.org/10.1016/j.febslet.2009.09.009
Bloch, Laura ; Sineshchekova, Olga ; Reichenbach, Daniela ; Reiss, Karina ; Saftig, Paul ; Kuro-o, Makoto ; Kaether, Christoph. / Klotho is a substrate for α-, β- and γ-secretase. In: FEBS Letters. 2009 ; Vol. 583, No. 19. pp. 3221-3224.
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