NEDD4 E3 ligase: Functions and mechanism in human cancer.

Abstract

A growing amount of evidence indicates that the neuronally expressed developmentally downregulated 4 (NEDD4, also known as NEDD4-1) E3 ligase plays a critical role in a variety of cellular processes via the ubiquitination-mediated degradation of multiple substrates. The abnormal regulation of NEDD4 protein has been implicated in cancer development and progression. In this review article, we briefly delineate the downstream substrates and upstream regulators of NEDD4, which are involved in carcinogenesis. Moreover, we succinctly elucidate the functions of NEDD4 protein in tumorigenesis and progression, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial mesenchymal transition (EMT), cancer stem cells, and drug resistance. The findings regarding NEDD4 functions are further supported by knockout mouse models and human tumor tissue studies. This review could provide a promising and optimum anticancer therapeutic strategy via targeting the NEDD4 protein.

• Authors: Zhi-Wei Wang, Xiaoli Hu, Miaomiao Ye, Min Lin, Man Chu, Xian Shen
• Journal: Seminars in cancer biology (Semin Cancer Biol) Vol. 67 Issue Pt 2 Pg. 92-101 (12 2020) ISSN: 1096-3650 [Electronic] England
• PMID: 32171886 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Nedd4 Ubiquitin Protein Ligases
• Nedd4 protein, human
• Nedd4 protein, mouse

Topics

• Animals
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Humans
• Mice, Knockout
• Molecular Targeted Therapy (methods)
• Nedd4 Ubiquitin Protein Ligases (genetics, metabolism)
• Neoplasms (genetics, metabolism, pathology)