A20 undermines alternative NF-?B activity and expression of anti-apoptotic genes in Helicobacter pylori infection.

A hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) pathways, underlying inflammation and cell survival. Here, we report that the classical NF-?B target gene product A20 contributes ...
to the negative regulation of alternative NF-?B signaling in gastric epithelial cells infected by H. pylori. Mechanistically, the de novo synthesized A20 protein interacts with tumor necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) and thereby interferes with the association of TIFA with the NIK regulatory complex. We also show that alternative NF-?B activity contributes to the up-regulation of anti-apoptotic genes, such as baculoviral IAP repeat containing 2 (BIRC2), BIRC3 and B-cell lymphoma 2-related protein A1 (BCL2A1) in gastric epithelial cells. Furthermore, the observed over-expression of RelB in human gastric biopsies with type B gastritis and RelB-dependent suppression of apoptotic cell death emphasize an important role of the alternative NF-?B pathway in H. pylori infection.
Mesh Terms:
Apoptosis Regulatory Proteins, Baculoviral IAP Repeat-Containing 3 Protein, Cell Line, Tumor, Gastric Mucosa, Gastritis, Gene Expression, Gene Knockout Techniques, Helicobacter Infections, Helicobacter pylori, Host-Pathogen Interactions, Humans, Minor Histocompatibility Antigens, NF-kappa B, Proto-Oncogene Proteins c-bcl-2, Signal Transduction, Transcription Factor RelA, Transcription Factor RelB, Tumor Necrosis Factor alpha-Induced Protein 3
Cell Mol Life Sci
Date: Jan. 28, 2022
Download Curated Data For This Publication
236076
Switch View:
  • Interactions 10