TIFA has dual functions in Helicobacter pylori-induced classical and alternative NF-kappa B pathways

Maubach G, Lim MCC, Sokolova O, Backert S, Meyer TF, Naumann M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

EMBO Reports EMBO Press

DOI: 10.15252/embr.202152878

Abstract

Helicobacter pylori infection constitutes one of the major risk factors for the development of gastric diseases including gastric cancer. The activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B) via classical and alternative pathways is a hallmark of H. pylori infection leading to inflammation in gastric epithelial cells. Tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA) was previously suggested to trigger classical NF-kappa B activation, but its role in alternative NF-kappa B activation remains unexplored. Here, we identify TRAF6 and TRAF2 as binding partners of TIFA, contributing to the formation of TIFAsomes upon H. pylori infection. Importantly, the TIFA/TRAF6 interaction enables binding of TGF beta-activated kinase 1 (TAK1), leading to the activation of classical NF-kappa B signaling, while the TIFA/TRAF2 interaction causes the transient displacement of cellular inhibitor of apoptosis 1 (cIAP1) from TRAF2, and proteasomal degradation of cIAP1, to facilitate the activation of the alternative NF-kappa B pathway. Our findings therefore establish a dual function of TIFA in the activation of classical and alternative NF-kappa B signaling in H. pylori-infected gastric epithelial cells.

Authors with CRIS profile

Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Max-Planck-Institut für Infektionsbiologie / Max Planck Institute for Infection Biology DE Germany (DE)

How to cite

APA:

Maubach, G., Lim, M.C.C., Sokolova, O., Backert, S., Meyer, T.F., & Naumann, M. (2021). TIFA has dual functions in Helicobacter pylori-induced classical and alternative NF-kappa B pathways. EMBO Reports. https://doi.org/10.15252/embr.202152878

MLA:

Maubach, Gunter, et al. "TIFA has dual functions in Helicobacter pylori-induced classical and alternative NF-kappa B pathways." EMBO Reports (2021).

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