NEDD4L Mediates ITGB4 Ubiquitination and Degradation to Suppress Esophageal Carcinoma Progression

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2024 Jun 3

PMID 38831335

Authors

Yijun Shi

Na Fang

Yutong Wu

Huiwen Xu

Anhui Ning

Wendi Zhang

Yiran Liu

Xiaobo Tao

Qiong Chen

Tian Tian

Lei Zhang

Minjie Chu

Jiahua Cui

Affiliations

Soon will be listed here.

Abstract

The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-β domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma.

Citing Articles

NEDD4L Suppresses Proliferation and Promotes Apoptosis by Ubiquitinating RAC2 Expression and Acts as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

Qi M, Tu J, He R, Fei X, Zhao Y Int J Mol Sci. 2024; 25(22).

PMID: 39596003 PMC: 11594477. DOI: 10.3390/ijms252211933.

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