Zhu, I.Y. orcid.org/0009-0004-2407-0297, Lloyd, A., Critchley, W.R. orcid.org/0000-0002-2707-4080 et al. (7 more authors) (2025) Structure and function of MDM2 and MDM4 in health and disease. The Biochemical journal, 482 (04). pp. 241-262. ISSN 0264-6021
Abstract
Both mouse double-minute 2 (MDM2), an E3 ubiquitin ligase, and its closely related paralog, MDM4, which lacks E3 activity, play central roles in cellular homeostasis. MDM-linked dysfunction is associated with an increased risk of oncogenesis, primarily through targeting the tumor suppressor protein p53 for ubiquitination and degradation. Recent studies have revealed multifaceted roles of MDM proteins that are p53 independent with implications for their oncogenic properties. This review aims to provide an overview of MDM2 and MDM4, by assessing gene and protein structure and implications for protein–protein interactions and functions in cell and animal physiology. We also explore MDM2 and MDM4 role(s) in angiogenesis, a critical feature of solid tumor growth and progression. Finally, we discuss the current landscape in the development of MDM2 and MDM4 inhibitors for cancer therapy.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
Keywords: | MDM2, MDM4, E3 ubiquitin ligase, p53, 26S proteasome, cancer |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cardiovascular Science (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Feb 2025 09:26 |
Last Modified: | 24 Feb 2025 09:26 |
Published Version: | https://portlandpress.com/biochemj/article/482/04/... |
Status: | Published |
Publisher: | Portland Press Ltd |
Identification Number: | 10.1042/bcj20240757 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223635 |