2. Academic Validation
  3. Structure and function of MDM2 and MDM4 in health and disease

Structure and function of MDM2 and MDM4 in health and disease

  • Biochem J. 2025 Feb 17;482(4):BCJ20240757. doi: 10.1042/BCJ20240757.
Ivy Yiyi Zhu 1,  Alec Lloyd 1,  William R Critchley 1,  Queen Saikia 1,  Dhananjay Jade 1 2,  Aysha Divan 1,  Elton Zeqiraj 1,  Michael A Harrison 1,  Christopher J Brown 3,  Sreenivasan Ponnambalam 1
Affiliations

Affiliations

  • 1 School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
  • 2 School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, U.K.
  • 3 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore.
PMID: 39960347 DOI: 10.1042/BCJ20240757
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.

Keywords

26S proteasome; E3 ubiquitin ligase; MDM2; MDM4; cancer; p53.

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