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Updated: Mar 23, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Published on: June 7, 2019

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Identification and characterization of BRAF⇔TP53 interactions in melanoma

Kayla T O'Toole1, Adamaris Martinez2, Brandon Murphy1

  • 1Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.

Cell Reports
|March 21, 2026
PubMed

Insights

Activating BRAF mutations in melanoma inhibit the tumor suppressor TP53 by binding its DNA-binding domain and moving it to the cytoplasm. This BRAF-TP53 interaction suppresses tumor suppressor activity without genetic alteration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Activating BRAF mutations are prevalent in cutaneous melanoma.
  • TP53 tumor suppressor inactivation is infrequent despite functional attenuation, suggesting alternative inhibition mechanisms.

Purpose of the Study:

  • To investigate the interaction between oncogenic BRAF and TP53.
  • To elucidate the mechanism by which BRAF inhibits TP53 function in melanoma.

Main Methods:

  • Proximity-dependent proteomic mapping to identify BRAF interactors.
  • Analysis of BRAF-TP53 interaction and TP53 subcellular localization.
  • Assessment of TP53 activity following DNA damage or pathway disruption.

Main Results:

  • A BRAFV600E-specific interactome was defined, revealing a selective interaction with TP53.
  • BRAFV600E binds the TP53 DNA-binding domain, promoting cytoplasmic localization and suppressing activity.
  • TP53 inhibition by BRAF persisted despite DNA damage or pharmacologic intervention.

Conclusions:

  • Oncogenic BRAFV600E functionally inactivates TP53 through direct protein interaction.
  • Melanoma can bypass TP53-mediated tumor suppression via BRAF-driven mechanisms, independent of genetic TP53 alteration.
Keywords:
BRAFCP: cancerTP53TurboIDcancermelanomaproteomics

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