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Updated: Jun 7, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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FBXO46 negatively regulates p53 activity by stabilizing Mdm2

Lai Wei1, Ning Yu1, Bo Yao1

  • 1Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.

FEBS Letters
|November 16, 2024
PubMed

Insights

F-box only protein 46 (FBXO46) stabilizes Mouse double minute 2 homolog (Mdm2), promoting the degradation of tumor suppressor p53. This FBXO46-Mdm2 interaction enhances cell proliferation and cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor p53 is crucial for preventing tumor formation.
  • Mouse double minute 2 homolog (Mdm2) targets p53 for ubiquitination and degradation.
  • Regulatory mechanisms of the Mdm2-p53 pathway require further elucidation.

Purpose of the Study:

  • To investigate the role of F-box only protein 46 (FBXO46) in the Mdm2-p53 pathway.
  • To understand how FBXO46 influences Mdm2 stability and activity.
  • To determine the functional consequences of FBXO46-mediated regulation of p53.

Main Methods:

  • Co-immunoprecipitation assays to confirm direct binding of FBXO46 to Mdm2.
  • Western blotting to assess Mdm2 and p53 protein levels and ubiquitination status.
  • Cell proliferation assays, cell cycle analysis, and anchorage-independent growth assays to evaluate cellular functions.

Main Results:

  • FBXO46 directly binds to Mdm2.
  • FBXO46 inhibits Mdm2 self-ubiquitination and degradation, leading to Mdm2 stabilization.
  • Stabilized Mdm2 promotes p53 ubiquitination and degradation, resulting in increased cell proliferation, accelerated G1/S cell cycle progression, and enhanced anchorage-independent growth.

Conclusions:

  • FBXO46 acts as a critical regulator of Mdm2 stability.
  • FBXO46 promotes oncogenic functions by inhibiting the p53 tumor suppressor pathway.
  • FBXO46 is a key player in controlling the Mdm2-p53 axis.
Keywords:
FBXO46Mdm2p53ubiquitination

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