1. Academic Validation
  2. β-catenin stimulates Tcf7l1 degradation through recruitment of casein kinase 2 in mouse embryonic stem cells

β-catenin stimulates Tcf7l1 degradation through recruitment of casein kinase 2 in mouse embryonic stem cells

  • Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287. doi: 10.1016/j.bbrc.2020.01.074.
Yan Zhang 1 Zhenhua Zhu 1 Huiwen Ding 1 Shengpeng Wan 1 Xinbao Zhang 1 Yuting Li 1 Junxiang Ji 1 Xin Wang 1 Meng Zhang 1 Shou-Dong Ye 2
Affiliations

Affiliations

  • 1 Center for Stem Cell and Translational Medicine, School of Life Sciences & Institute of Physical Science and Information Technology, Anhui University, Hefei, 230601, PR China.
  • 2 Center for Stem Cell and Translational Medicine, School of Life Sciences & Institute of Physical Science and Information Technology, Anhui University, Hefei, 230601, PR China. Electronic address: shdye@126.com.
Abstract

Activation of the Wnt/β-catenin signaling pathway by the inhibition of glycogen synthase kinase-3 (GSK-3) will induce Tcf7l1 protein degradation to effectively promote embryonic stem cell (ESC) self-renewal. However, the exact mechanism remains unclear. Here, we found that inhibition of Casein Kinase 2 (Csnk2) by TBB or DMAT was sufficient to block the reduction of the Tcf7l1 protein induced by CHIR99021, a specific inhibitor of GSK-3. Similarly, downregulation of Csnk2 increased the Tcf7l1 level. In contrast, overexpression of Csnk2 significantly decreased Tcf7l1 protein stability in mouse ESCs. Notably, Csnk2α1 controls Tcf7l1 turnover to a greater degree than the other two isoforms of Csnk2, Csnk2α2 and Csnk2β, as Csnk2α1-overexpressing mouse ESCs exhibited the lowest level of Tcf7l1. Csnk2α1 interacted with and phosphorylated Tcf7l1. In addition, the association of Csnk2α1 and Tcf7l1 was enhanced by CHIR99021. Our study demonstrated, for the first time, that Csnk2 is involved in Tcf7l1 turnover mediated by the Wnt/β-catenin signaling pathway. These results expand our understanding of the function and circuit of Wnt/β-catenin signaling pathway in ESCs.

Keywords

Csnk2; Degradation; Embryonic stem cells; Tcf7l1; β-catenin.

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