Arginine methylation of the c-Jun coactivator RACO-1 is required for c-Jun/AP-1 activation

Clare C Davies1, Atanu Chakraborty, Markus E Diefenbacher

  • 1Mammalian Genetics Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.

The EMBO Journal
|April 30, 2013
PubMed

Insights

Arginine methylation of RACO-1 by PRMT1 is crucial for c-Jun/AP-1 transcription factor activity. This process stabilizes RACO-1, enabling dimer formation and interaction with c-Jun, impacting gene expression.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • c-Jun is a key component of the AP-1 transcription factor complex, regulating cellular proliferation and oncogenic transformation.
  • RACO-1, a RING domain protein, acts as a c-Jun coactivator, linking growth factor signaling to AP-1 transactivation.

Purpose of the Study:

  • To investigate the role of RACO-1 post-translational modifications in c-Jun/AP-1 complex formation and function.
  • To identify the specific enzymes and mechanisms involved in regulating RACO-1 activity.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • In vitro methylation assays using purified PRMT1 and RACO-1.
  • Western blotting to detect protein modifications and ubiquitination.
  • Quantitative PCR to assess target gene expression.

Main Results:

  • RACO-1 exists as a nuclear dimer and specifically interacts with dimeric RACO-1.
  • PRMT1 methylates RACO-1 on two arginine residues, stabilizing the protein via K63-linked ubiquitination.
  • Methylation facilitates RACO-1 dimerization and c-Jun interaction.
  • Inhibition of PRMT1 impairs AP-1 activity and reduces the expression of numerous c-Jun target genes.

Conclusions:

  • Arginine methylation of RACO-1 by PRMT1 is essential for efficient transcriptional activation by c-Jun/AP-1.
  • PRMT1 is identified as a critical regulator of c-Jun/AP-1 function, impacting cellular processes like proliferation and transformation.

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