After the Akt-induced phosphorylation of either Ser21 (α) or Ser9 (β) in N-terminal regulatory domains in response to PI3K-mediated signaling, GSK3 (both GSH3α and GSK3β) is inactivated and targeted for proteasomal degradation.86,90 The Akt-mediated phosphorylation of GSK3 produces an intramolecular pseudosubstrate that blocks the binding pocket and inhibits the substrate from approaching GSK3.91 GSK3 expression affects various biochemical processes in cancer. The gene discussed is AKT1; the disease is cancer.