2. Academic Validation
  3. Tau acetylates and stabilizes β-catenin thereby promoting cell survival

Tau acetylates and stabilizes β-catenin thereby promoting cell survival

  • EMBO Rep. 2020 Mar 4;21(3):e48328. doi: 10.15252/embr.201948328.
Enjie Liu  # 1 2,  Qiuzhi Zhou  # 1,  Ao-Ji Xie 1,  Xiaoguang Li 1,  Mengzhu Li 1,  Jinwang Ye 1,  Shihong Li 1,  Dan Ke 1,  Qun Wang 1,  Zhi-Peng Xu 1,  Li Li 1,  Ying Yang 1,  Gong-Ping Liu 1,  Xiao-Chuan Wang 1,  Hong-Lian Li 3,  Jian-Zhi Wang 1 4
Affiliations

Affiliations

  • 1 Key Laboratory of Ministry of Education of China for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Key Laboratory of Ministry of Education of China for Neurological Disorders, Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • # Contributed equally.
PMID: 31930681 DOI: 10.15252/embr.201948328
Abstract

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.

Keywords

Tau; acetylation; acetyltransferase; anti-apoptosis; β-catenin.

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