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Liu, Enjie; Zhou, Qiuzhi; Xie, Ao‐Ji; Li, Xiaoguang; Li, Mengzhu; Ye, Jinwang; Li, Shihong; Ke, Dan; Wang, Qun; Xu, Zhi‐Peng; Li, Li; Yang, Ying; Liu, Gong‐Ping; Wang, Xiao‐Chuan; Li, Hong‐Lian; Wang, Jian‐Zhi
EMBO reports, 04 March 2020, Letnik: 21, Številka: 3Journal Article
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. Synopsis Tau acetylates β‐catenin at K49, which stabilizes β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis. β‐catenin mediates the anti‐apoptotic effects of Tau by increasing the expression of survival‐promoting genes. Tau can acetylate β‐catenin at K49 in a concentration‐, time‐ pH‐ and acetyltransferase domain‐dependent manner. K49‐acetylation by Tau preserves β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis, resulting in increased nuclear translocation and enhanced transcriptional activity of β‐catenin. β‐catenin K49‐acetylation mediates the anti‐apoptotic effects of Tau by augmenting the expression of survival‐promoting genes. Tau acetylates β‐catenin at K49, which stabilizes β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis. β‐catenin mediates the anti‐apoptotic effects of Tau by increasing the expression of survival‐promoting genes.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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