[摘要]:Protein phosphatase-2A (PP2A) activity, which is compromised in Alzheimer disease brain, is regulated by two endogenous inhibitors, one of them being I-2(PP2A), a 277 amino acid long protein also known as SET. Here we report that both the amino terminal fragment (I-2NTF; aa 1-175) and the carboxy terminal fragment (I-2CTF; aa 176-277) of I-2PP2A inhibit PP2A by binding to its catalytic subunit PP2Ac and cause hyperphosphorylation of tau. The C-terminal acidic region in I-2CTF and Val 92 in I-2NTF are essential for their association with PP2Ac and inhibition of the phosphatase activity. Structured summary of protein interactions: I2PP2A physically interacts with PP2A-C by anti tag coimmunoprecipitation (view interaction 1, 2) I2PP2A physically interacts with PP2A-C by pull down (view interaction 1, 2) PP2A-A physically interacts with PP2A-B and PP2A-C by pull down (view interaction) (C) 2011 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.