Article
- The EMBO Journal (2006) 25, 5094 - 5104
- doi:10.1038/sj.emboj.7601389
Published online: 19 October 2006
Subject Categories:
Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation
M D Mostaqul Huq1, Pawan Gupta1, Nien-Pei Tsai1, Roger White2, Malcolm G Parker2 and Li-Na Wei1
- Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA
- Institute of Reproductive and Developmental Biology, Imperial College London, London, UK
Correspondence to:
Li-Na Wei, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455-0217, USA. Tel.: +1 612 625 9402; Fax: +1 612 625 8408; E-mail: weixx009@umn.edu
Received 8 June 2005; Accepted 12 September 2006
Abstract
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.
Keywords:
- CRM1,
- HDACs,
- nuclear export,
- protein arginine methylation,
- RIP140
