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Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation
Author(s) -
Mostaqul Huq M D,
Gupta Pawan,
Tsai NienPei,
White Roger,
Parker Malcolm G,
Wei LiNa
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601389
Subject(s) - medical school , white (mutation) , library science , biology , gerontology , medicine , genetics , medical education , gene , computer science
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.