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

Clare C Davies, Atanu Chakraborty, Markus E Diefenbacher, Mark Skehel, Axel Behrens

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1556-67
Number of pages12
JournalThe EMBO journal
Volume32
Issue number11
DOIs
Publication statusPublished - 29 May 2013

Keywords

  • Animals
  • Arginine
  • Cell Nucleus
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Dimerization
  • HEK293 Cells
  • Humans
  • Methylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Arginine N-Methyltransferases
  • Proto-Oncogene Proteins c-jun
  • Rabbits
  • Repressor Proteins
  • Signal Transduction
  • Trans-Activators
  • Transcription Factor AP-1
  • Transcriptional Activation
  • Ubiquitin-Protein Ligases

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