Tau acetylates and stabilizes β‐catenin thereby promoting cell survival

Abstract

Overexpressing Tau counteracts apoptosis and increases dephos- phorylated b-catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate b-catenin at K49 in a concentration-, time-, and pH-dependent manner. b-catenin K49 acetylation inhibits its phosphorylation and its ubiquitination-associated proteolysis, thus increasing b-catenin protein levels. K49 acetylation further promotes nuclear transloca- tion and the transcriptional activity of b-catenin, and increases the expression of survival-promoting genes (bcl2 and survivin), coun- teracting apoptosis. Mutation of Tau’s acetyltransferase domain or co-expressing non-acetylatable b-catenin-K49R prevents increased b-catenin signaling and abolishes the anti-apoptotic function of Tau. Our data reveal that Tau preserves b-catenin by acetylating K49, and upregulated b-catenin/survival signaling in turn mediates the anti-apoptotic effect of Tau. Keywords