FIG 9.

Schematic model of regulation of ribosomal biogenesis. Canonical regulation of β-catenin is mediated by Wnt ligand binding to its cognate receptor, Frizzled, leading to the phosphorylation and inactivation of GSK3β and the stabilization of β-catenin. Nuclear translocation of β-catenin transcriptionally activates target genes, including cMYC, which in turn induces ribosomal biogenesis and protein synthesis. During hyperammonemia, noncanonical regulation via GSK3β-independent, IKKβ-dependent phosphorylation and degradation of β-catenin results in impaired ribosomal biogenesis and protein synthesis.