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Tau acetylates and stabilizes β‐catenin thereby promoting cell survival
Author(s) -
Liu Enjie,
Zhou Qiuzhi,
Xie AoJi,
Li Xiaoguang,
Li Mengzhu,
Ye Jinwang,
Li Shihong,
Ke Dan,
Wang Qun,
Xu ZhiPeng,
Li Li,
Yang Ying,
Liu GongPing,
Wang XiaoChuan,
Li HongLian,
Wang JianZhi
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948328
Subject(s) - acetylation , catenin , survivin , phosphorylation , ubiquitin , microbiology and biotechnology , apoptosis , acetyltransferase , downregulation and upregulation , proteolysis , biology , beta catenin , signal transduction , chemistry , wnt signaling pathway , gene , biochemistry , enzyme
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.