title: The intracellular domain of amyloid precursor protein interacts with FKBP12.
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 Abeta 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.
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei, 10051, Taiwan, ROC.
authors.forename: Fan-Lun
authors.initials: FL
authors.lastname: Liu
authors.forename: Pei-Hsueh
authors.initials: PH
authors.lastname: Liu
authors.forename: Hsien-Wei
authors.initials: HW
authors.lastname: Shao
authors.forename: Fan-Lu
authors.initials: FL
authors.lastname: Kung
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D047468:Immunoprecipitation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000032:analysis; D022061:Tacrolimus Binding Protein 1A / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D016564:Amyloid beta-Protein Precursor; D011993:Recombinant Fusion Proteins; D022061:Tacrolimus Binding Protein 1A