4.7 Article

USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 79, Issue 8, Pages -

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-022-04489-7

Keywords

Apoptotic cell death; COP9 signalosome (CSN); Deubiquitinylase (DUB); Nedd8; RelA

Funding

  1. German Research Foundation [RTG 2408-361210922, CRC 854-97850925]
  2. Projekt DEAL

Ask authors/readers for more resources

Helicobacter pylori infection is associated with the development of gastric diseases, including cancer. NF-κB and DUB USP48 play important roles in this process. USP48 stabilizes NF-κB activity by deubiquitination, enhancing its transcriptional activity and reducing apoptotic cell death. This finding provides new insights into the cell survival mechanism in H. pylori infection.
The human pathogen Helicobacter pylori represents a risk factor for the development of gastric diseases including cancer. The H. pylori-induced transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) is involved in the pro-inflammatory response and cell survival in the gastric mucosa, and represents a trailblazer of gastric pathophysiology. Termination of nuclear NF-kappa B heterodimer RelA/p50 activity is regulated by the ubiquitin-RING-ligase complex elongin-cullin-suppressor of cytokine signalling 1 (ECSSOCS1), which leads to K48-ubiquitinylation and degradation of RelA. We found that deubiquitinylase (DUB) ubiquitin specific protease 48 (USP48), which interacts with the COP9 signalosome (CSN) subunit CSN1, stabilises RelA by deubiquitinylation and thereby promotes the transcriptional activity of RelA to prolong de novo synthesis of DUB A20 in H. pylori infection. An important role of A20 is the suppression of caspase-8 activity and apoptotic cell death. USP48 thus enhances the activity of A20 to reduce apoptotic cell death in cells infected with H. pylori. Our results, therefore, define a synergistic mechanism by which USP48 and A20 regulate RelA and apoptotic cell death in H. pylori infection.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available