title: 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.
abstract: 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.
authors.affiliation: Medical School, Xiamen University, Fujian, China. chunxia@xmu.edu.cn
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Xia
mesh_terms: D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D025801:Ubiquitin; D010768:Phosphoserine; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate