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Updated: Sep 24, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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The Mettl3 epitranscriptomic writer amplifies p53 stress responses

Nitin Raj1, Mengxiong Wang1, Jose A Seoane2

  • 1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Molecular Cell
|May 5, 2022
PubMed

Insights

The study reveals METTL3 amplifies p53 tumor suppressor activity by stabilizing the p53 protein. This interaction is crucial for anti-proliferative gene expression and tumor suppression, particularly in response to cellular stress.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The p53 transcription factor is a critical regulator of cellular responses to stress, including DNA damage and oncogenic signaling.
  • p53 induces anti-proliferative gene expression programs that are essential for tumor suppression.

Purpose of the Study:

  • To identify novel mechanisms by which p53 regulates gene expression.
  • To investigate the role of p53-interacting proteins in cellular stress responses.

Main Methods:

  • Tandem affinity purification coupled with mass spectrometry (TAP-MS) to identify p53-interacting proteins.
  • In vitro and in vivo experiments using mouse cancer models and human cancer cells.
  • Analysis of human cancer genome data.

Main Results:

  • METTL3, a component of the m6A RNA methyltransferase complex (MTC), was identified as a p53 interactor.
  • METTL3 enhances p53 protein stabilization and target gene expression in response to DNA damage and oncogenic signals through both catalytic-dependent and independent mechanisms.
  • METTL3 promotes p53 tumor suppressor activity in vivo and in human cancer cells, but only when p53 is intact.
  • MTC components reinforce p53 function in human cancer.

Conclusions:

  • METTL3 plays a fundamental role in amplifying p53 signaling pathways in response to cellular stress.
  • The METTL3-p53 interaction represents a novel mechanism for regulating tumor suppressor activity.
  • Targeting the METTL3-p53 axis may offer new therapeutic strategies for cancer treatment.
Keywords:
DNA damageMETTL14METTL3N(6)-methyladenosine (m6A) modificationepitranscriptomicslung cancermass spectrometrymethyltransferase complexp53tumor suppressor

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