Overexpressing Tau counteracts apoptosis and increases dephosphorylated β-catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate β-catenin at K49 in a concentration-, time-, and pH-dependent manner. β-catenin K49 acetylation inhibits its phosphorylation and its ubiquitination-associated proteolysis, thus increasing β-catenin protein levels. K49 acetylation further promotes nuclear translocation and the transcriptional activity of β-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 β-catenin-K49R prevents increased β-catenin signaling and abolishes the anti-apoptotic function of Tau. Our data reveal that Tau preserves β-catenin by acetylating K49, and upregulated β-catenin/survival signaling in turn mediates the anti-apoptotic effect of Tau.

中文翻译：

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Tau 乙酰化并稳定 β-连环蛋白，从而促进细胞存活。

过表达 Tau 会抵消细胞凋亡并增加去磷酸化的 β-连环蛋白水平，但潜在的机制是难以捉摸的。在这里，我们表明 Tau 可以在 K49 处以浓度、时间和 pH 依赖的方式直接和稳健地乙酰化 β-连环蛋白。β-catenin K49 乙酰化抑制其磷酸化及其泛素化相关蛋白水解，从而增加 β-catenin 蛋白水平。K49 乙酰化进一步促进核转位和 β-连环蛋白的转录活性，并增加存活促进基因（bcl2 和 survivin）的表达，从而抑制细胞凋亡。Tau 的乙酰转移酶结构域的突变或共表达非乙酰化 β-连环蛋白-K49R 可防止增加的 β-连环蛋白信号传导并消除 Tau 的抗凋亡功能。我们的数据表明，Tau 通过乙酰化 K49 来保留 β-连环蛋白，