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.