Phosphorylation of SET mediates apoptosis via P53 hyperactivation and NM23-H1 nuclear import.

Apoptosis plays an important role in neuron loss in Alzheimer's disease (AD). SET, an endogenous inhibitor of protein phosphatase-2A, is phosphorylated in AD brains and positively correlates with cell apoptosis. However, the mechanism underlying phosphorylated SET association with apoptosis remains unknown.

Ser9 phosphorylation causes cytoplasmic detention of I2PP2A/SET in Alzheimer disease.

The nuclear protein I2(PP2A)/SET, an endogenous inhibitor of protein phosphatase-2A (PP2A), is increased and translocated to the cytoplasm in the neurons of Alzheimer's disease (AD) brains, and PP2A activity in cytoplasm is compromised. However, it is not fully understood how SET is retained in the cytoplasm. By generating a phosphorylation site-specific antibody, we found in the present study that SET is phosphorylated at Ser9, by which it is accumulated in the cytoplasm of the AD brains.