SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitive impairments.

ABSTRACT: PP2A is a major regulator of tau phosphorylation, which is principally regulated by an endogenous nuclear protein inhibitor 2 of PP2A (I₂^PP2A), also named SET. However, how SET is post-translationally regulated and translocates from the nucleus to the cytoplasm remain incompletely understood. Here we show SET is SUMOylated at K68 residue that induces its cytoplasmic retention, resulting in Alzheimer disease (AD) like tau pathology and cognitive defects. SET is predominantly SUMOylated at K68 that leads to its translocation from the nucleus to the cytoplasm and subsequently induces inhibition of PP2A and hyperphosphorylation of tau in HEK-293 cells. Moreover, overexpression of wild type SET significantly inhibits PP2A activity, leading to tau hyperphosphorylation, less

SUBMITTER: Qin M 

PROVIDER: S-EPMC6376727 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature