Due to its fundamental role in all eukaryotic cells, a deeper understanding of the molecular mechanisms underlying ubiquitination is of central importance. Being responsible for chain specificity and substrate recognition, E3 ligases are the selective elements of the ubiquitination process. In this review, we discuss different cellular pathways regulated by one of the first identified E3 ligase, NEDD4, focusing on its pathophysiological role, its known targets and modulators. In addition, we highlight small molecule inhibitors that act on NEDD4 and discuss new strategies to effectively target this E3 enzyme.
Keywords: E3 ubiquitin-protein ligase NEDD4; cancer; enzyme activity; metabolism; ubiquitin signaling.
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.