A transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60

Amyloid-beta precursor protein (APP) a widely expressed cell-surface protein. is cleaved in the transmembrane region by gamma -secretase, gamma -Cleavage Of APP produces the extracellular amyloid beta -peptide of Alzheimer's disease and releases an intracellular tail fragment of unknown physiological function. We now demonstrate that the cytoplasmic tail of APP forms a multimeric complex with the nuclear adaptor protein Fe65 and the histone acetyltransferase Tip60. This complex potently stimulates transcription via heterologous Gal4- or LexA-DNA binding domains, suggesting that release of the cytoplasmic tail of APP by gamma -cleavage may function in gene expression.