|
Figure 1
Simplified schematic overview of lithium effects on GSK3β, eIF2B, and β-catenin. Lithium inhibits GSK3β activity. GSK3β inhibition lowers eIF2B phosphorylation (yellow) levels resulting in increased eIF2B activity and presumably downregulated expression of ATF4 and the ATF4-regulated transcriptome. GSK3β inhibition also stabilizes β-catenin by impeding its phosphorylation (yellow) at Ser33, Ser37, and Thr41. Phosphorylated β-catenin is highly unstable and was therefore not quantified. Non-phosphorylated β-catenin moves to the nucleus and joins with a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors. This joining upregulates the expression of several genes, including