The intracellular domain of amyloid precursor protein interacts with FKBP12
Journal
Biochemical and Biophysical Research Communications
Journal Volume
350
Journal Issue
2
Pages
472-477
Date Issued
2006
Author(s)
Abstract
To elucidate the roles of the APP intracellular domain (AICD) in the development of Alzheimer's disease, a yeast two-hybrid system was used to screen for AICD-interacting proteins. Our result revealed that FKBP12, an immunophilin with a peptidyl-prolyl cis-trans isomerase (PPIase) activity, may interact with AICD. This interaction was confirmed by coimmunoprecipitation studies. FKBP12 has been shown to be expressed at a higher level in areas of pathology of patients with neurodegenerative diseases. In addition, Pin1, a member of another PPIase family, has been suggested to be involved in the amyloidogenic APP processing and Aβ production. The interaction between FKBP12 and AICD might hint at a possible role FKBP12 plays, probably in a fashion similar to Pin1, in the amyloidogenesis of APP. We also found that the interaction was interfered, in a dose-dependent manner, by FK506, whose neuroprotective effect has been suggested to be correlated with its PPIase inhibitory activity. ? 2006 Elsevier Inc. All rights reserved.
Subjects
AICD (APP intracellular domain); Alzheimer's disease; FK506; FKBPs
SDGs
Other Subjects
amyloid beta protein; amyloid precursor protein; cyclophilin; fk 506 binding protein; tacrolimus; Alzheimer disease; article; concentration response; controlled study; correlation analysis; degenerative disease; enzyme activity; enzyme inhibition; human; human cell; immunoprecipitation; neuroprotection; nucleotide sequence; pathology; priority journal; protein domain; protein expression; protein function; protein interaction; screening; Amyloid beta-Protein Precursor; Binding Sites; Humans; Immunoprecipitation; Protein Structure, Tertiary; Recombinant Fusion Proteins; Tacrolimus Binding Protein 1A; Two-Hybrid System Techniques
Type
journal article