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Updated: May 11, 2026

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
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.
Abstract:
c-Jun, the major component of the AP-1 transcription factor complex, has important functions in cellular proliferation and oncogenic transformation. The RING domain-containing protein RACO-1 functions as a c-Jun coactivator that molecularly links growth factor signalling to AP-1 transactivation. Here we demonstrate that RACO-1 is present as a nuclear dimer and that c-Jun specifically interacts with dimeric RACO-1. Moreover, RACO-1 is identified as a substrate of the arginine methyltransferase PRMT1, which methylates RACO-1 on two arginine residues. Arginine methylation of RACO-1 promotes a conformational change that stabilises RACO-1 by facilitating K63-linked ubiquitin chain formation, and enables RACO-1 dimerisation and c-Jun interaction. Abrogation of PRMT1 function impairs AP-1 activity and results in decreased expression of a large percentage of c-Jun target genes. These results demonstrate that arginine methylation of RACO-1 is required for efficient transcriptional activation by c-Jun/AP-1 and thus identify PRMT1 as an important regulator of c-Jun/AP-1 function.
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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