12-O-tetradecanoylphorbol-1,3-acetate-induced degradation of protein kinase B via ubiquitin-proteasomal pathway depends on its Ser473 phosphorylation in gastric cancer cells.

TPA (12-O-tetradecanoylphorbol-1, 3-acetate) can induce cell apoptosis and cause PKB (protein kinase B) degradation correlated with its phosphorylation in gastric cancer cells. We investigated whether the ubiquitin-proteasomal pathway is involved in TPA-induced PKB degradation. The results showed that TPA could induce PKB ubiquitination by inhibiting its phosphorylation at the serine 473 site. Moreover, MG132 (26S proteasome inhibitor) partially inhibited TPA-induced degradation of PKB. Taken together, TPA could degrade PKB via the ubiquitin-proteasomal pathway, and the suppression of PKB phosphorylation at the serine 473 site might be a prerequisite for the TPA-induced ubiquitination in gastric cancer cells.