Tau acetylates and stabilizes β‐catenin thereby promoting cell survival

Abstract

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