Fig. 7: Schematic showing that ZDHHC4-mediated GSK3β palmitoylation promotes GBM TMZ-resistance.

ZDHHC4 palmitoylates GSK3β and competitively binds GSK3β with AKT and p70S6K kinases, which inhibits GSK3β Ser9 phosphorylation and enhances GSK3β Tyr216 phosphorylation. Activated GSK3β enhances GSC self-renewal, GBM TMZ-resistance, and tumorigenesis by promoting the EZH2/STAT3 axis.