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Structure and function of MDM2 and MDM4 in health and disease

Ivy Yiyi Zhu1, Alec Lloyd1, William R Critchley1

  • 1School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.

The Biochemical Journal
|February 17, 2025
PubMed

Insights

Mouse double-minute 2 (MDM2) and MDM4 proteins regulate cellular homeostasis and are implicated in cancer development. This review covers their roles, p53-independent functions, and therapeutic inhibition strategies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Mouse double-minute 2 (MDM2) and MDM4 are crucial regulators of cellular homeostasis.
  • Dysfunction of MDM proteins is linked to oncogenesis, often via the tumor suppressor p53.
  • Emerging evidence highlights p53-independent roles of MDM proteins in cancer.

Purpose of the Study:

  • To provide a comprehensive overview of MDM2 and MDM4.
  • To assess their gene and protein structure, interactions, and physiological functions.
  • To explore their roles in angiogenesis and discuss therapeutic inhibitor development.

Main Methods:

  • Literature review and analysis of existing studies on MDM2 and MDM4.
  • Assessment of gene and protein structures and their functional implications.
  • Examination of roles in angiogenesis and current therapeutic strategies.

Main Results:

  • MDM2 and MDM4 are key regulators of p53, a critical tumor suppressor.
  • MDM proteins exhibit p53-independent functions contributing to oncogenesis.
  • MDM2 and MDM4 play significant roles in angiogenesis, vital for tumor growth.

Conclusions:

  • MDM2 and MDM4 are central to cellular homeostasis and oncogenesis.
  • Understanding their p53-dependent and independent functions is critical for cancer research.
  • Targeting MDM2 and MDM4 presents a promising avenue for novel cancer therapies.
Keywords:
26S proteasomeE3 ubiquitin ligaseMDM2MDM4cancerp53

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