Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori–infected gastric epithelial cancer cells

What is it about?

We show that the E3 ubiquitin ligase Siah2 gets acetylated by p300 in the H. pylori-infected gastric epithelial cell lines. Acetylation-mediated stabilization of Siah2 efficiently degrades prolyl hydroxylase 3 (PHD3) in the infected gastric epithelium. PHD3 degradation causes accumulation of the oncogenic transcription factor hypoxia-inducible factor 1 alpha (Hif1a). As a result, infected cells show increased invasiveness. The same phenomenon is observed in H. felis-infected mouse gastric epithelia and human gastric cancer biopsy samples. This study establishes for the first time that ac-Siah2 is crucial in increasing the invasiveness of H. pylori-infected gastric cancer cells.

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