An X11α/FSBP complex represses transcription of the GSK3β gene promoter

Abstract

X11α is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Aβ peptide that is deposited in Alzheimer's disease brains. X11α also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11α interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11α/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3β promoter activity. Glycogen synthase kinase-3β is a favoured candidate kinase for phosphorylating tau in Alzheimer's disease. Our findings show a new function for X11α that may impact on Alzheimer's disease pathogenesis.