YWHAE is a novel interaction partner of Helicobacter pylori CagA.

CagA, an important virulence factor of Helicobacter pylori, targets and interacts with a series of host proteins to activate signaling factors involved in many functions, such as development, cytoskeleton rearrangement and inflammatory molecule release. Despite extensive efforts, the relationship between CagA and gastric cancer is far from completely understood. Here, the GAL4 yeast two-hybrid system was used to screen cellular proteins for binding to CagA, and five cellular proteins, including tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon (YWHAE), were identified. The CagA-YWHAE interaction was further verified not only in vitro by a glutathione S-transferase pull-down assay, but also in vivo by immunolocalization and co-immunoprecipitation assays. In SGC7901 and AGS cells, overexpression of the YWHAE protein promoted the activation of NF-κB by CagA; conversely, knockdown of the YWHAE protein inhibited the activation of NF-κB by CagA. These results indicate that CagA enhances the YWHAE-mediated transactivation of NF-κB, providing a new clue to the molecular mechanisms of H. pylori-associated tumorigenesis mediated by CagA.