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 (PP2A), is phosphorylated in AD brains and positively correlates with cell apoptosis. However, the mechanism underlying phosphorylated SET association with apoptosis remains unknown. Here we show that mimetic phosphorylation o f SET (S9E) induced apoptosis of primary cultured neurons. To investigate its mechanism, we overexpressed SET (S9E) in HEK 293/tau cells and observed apoptosis accompanied with a marked increase of cleaved caspase-3 and cytoplasmic SET (S9E) retention with enhanced PP2A inhibition, which subsequentl y caused p53 hyperphosphorylation and activation.

Source: Neurobiology of Aging - May 8, 2018 Category: Neuroscience Authors: Mengjuan Wu, Guang Yu, Tonghai Yan, Dan Ke, Qun Wang, Rong Liu, Jian-Zhi Wang, Bin Zhang, Dan Chen, Xiaochuan Wang Source Type: research