Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation

M. D.Mostaqul Huq, Pawan Gupta, Nien Pei Tsai, Roger White, Malcolm G. Parker, Li-Na Wei

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84 Scopus citations


Receptor interacting protein 140 (RIP140), a ligand-dependent corepressor for nuclear receptors, can be modified by arginine methylation. Three methylated arginine residues, at Arg-240, Arg-650, and Arg-948, were identified by mass spectrometric analysis. Site-directed mutagenesis studies demonstrated the functionality of these arginine residues. The biological activity of RIP140 was suppressed by protein arginine methyltransferase 1 (PRMT1) due to RIP140 methylation, which reduced the recruitment of histone deacetylases to RIP140 and facilitated its nuclear export by enhancing interaction with exportin 1. A constitutive negative (Arg/Ala) mutant of RIP140 was resistant to the effect of PRMT1, and a constitutive positive (Arg/Phe) mutation mimicked the effect of arginine methylation. The biological activities of the wild type and the mutant proteins were examined in RIP140-null MEF cells. This study uncovered a novel means to inactivate, or suppress, RIP140, and demonstrated protein arginine methylation as a critical type of modification for corepressor.

Original languageEnglish (US)
Pages (from-to)5094-5104
Number of pages11
JournalEMBO Journal
Issue number21
StatePublished - Nov 1 2006


  • CRM1
  • HDACs
  • Nuclear export
  • Protein arginine methylation
  • RIP140


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