YWHAE is a novel interaction partner of Helicobacter pylori CagA
Xiaoyan Zhang1,2, Bangwei Zeng1,2,3, Chunyan Wen1,2
1Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, 1 Xuefu North Road, University Town, Fuzhou, Fujian Province 350122, PR China.
Abstract:
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.
Insights
Helicobacter pylori CagA protein interacts with YWHAE, enhancing NF-κB activation. This CagA-YWHAE interaction offers new insights into H. pylori-induced gastric cancer development.
Area of Science:
- Microbiology
- Molecular Biology
- Oncology
Background:
- Helicobacter pylori CagA is a key virulence factor implicated in gastric diseases.
- The precise molecular mechanisms linking CagA to gastric cancer remain incompletely understood.
Purpose of the Study:
- To identify host proteins interacting with CagA.
- To elucidate the role of CagA-host protein interactions in NF-κB signaling and gastric tumorigenesis.
Main Methods:
- GAL4 yeast two-hybrid system for screening CagA-interacting proteins.
- In vitro (GST pull-down) and in vivo (immunolocalization, co-immunoprecipitation) assays to validate interactions.
- Cell-based assays (overexpression, knockdown) to assess NF-κB activation.
Main Results:
- Identified YWHAE (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon) as a CagA-interacting protein.
- Confirmed CagA-YWHAE interaction in vitro and in vivo.
- Demonstrated that YWHAE mediates CagA-induced NF-κB activation; YWHAE overexpression enhanced it, while knockdown inhibited it.
Conclusions:
- CagA enhances YWHAE-mediated transactivation of NF-κB.
- This interaction provides a novel molecular mechanism contributing to H. pylori-associated gastric cancer.
More Related Videos
09:05High Resolution Electron Microscopy of the Helicobacter pylori Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability
Published on: November 21, 2014
03:47Retinal and Choroidal Thickness Changes in Populations with Helicobacter pylori Infection by Swept-Source Optical Coherence Tomography
Published on: November 1, 2024
Related Concept Videos
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
01:30Peptic Ulcer Disease I: Introduction
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
01:28Peptic Ulcer Disease II: Pathophysiology
Damaging agents such as Helicobacter pylori, gastric acid, pepsin, and nonsteroidal anti-inflammatory drugs (NSAIDs) can weaken the mucosal defense, allowing hydrogen ions to infiltrate back and harm epithelial cells.
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
01:22Pathophysiology of Peptic Ulcer Disease: Injurious Factors
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
01:26Peptic Ulcer Disease IV: Management
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...