Related Experiment Video

Updated: Aug 3, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K

Interactome dynamics of RAF1-BRAF kinase monomers and dimers

Luis F Iglesias-Martinez1, Nora Rauch1, Kieran Wynne1

  • 1Systems Biology Ireland, School of Medicine, University College Dublin, Dublin, Ireland.

Scientific Data
|April 12, 2023
PubMed

Insights

RAF kinases are key in cancer, but inhibitors can cause resistance via RAF1-BRAF dimerization. This study maps protein interactions to understand RAF signaling and drug resistance mechanisms.

Area of Science:

  • Molecular Biology
  • Oncology
  • Proteomics

Background:

  • RAF kinases are crucial in cell signaling and cancer development.
  • BRAFV600E mutations drive approximately 6% of human cancers.
  • Current RAF inhibitors have variable efficacy and can induce paradoxical activation, often linked to RAF1-BRAF dimerization.

Purpose of the Study:

  • To map the interactomes of RAF1 monomers and RAF1-BRAF/BRAFV600E dimers.
  • To investigate the impact of RAF inhibitors (vemurafenib, sorafenib) on these interactomes.
  • To elucidate the role of dynamic interactome changes in RAF signaling and drug resistance.

Main Methods:

  • Quantitative proteomics to identify and quantify interacting proteins.
  • Analysis of RAF1 monomers, RAF1-BRAF dimers, and RAF1-BRAFV600E dimers.
  • Comparative analysis using regression to assess interactome differences under various conditions, including drug treatment.

Main Results:

  • Identified and quantified over 1,000 proteins in the RAF interactomes.
  • Revealed a substantial overlapping core interactome across different RAF states.
  • Detected distinct, condition-specific differences in protein interactions, influenced by dimerization and drug treatment.

Conclusions:

  • Dynamic changes in the RAF interactome, including kinase-independent functions, contribute to functional diversification.
  • Understanding these interactome dynamics is vital for deciphering RAF signaling pathways.
  • This research provides insights into mechanisms of resistance to RAF inhibitors, potentially guiding future therapeutic strategies.

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