Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation.
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.
Mostaqul Huq
M D
MD
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455-0217, USA.
Gupta
Pawan
P
Tsai
Nien-Pei
NP
White
Roger
R
Parker
Malcolm G
MG
Wei
Li-Na
LN
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
D048868:Adaptor Proteins, Signal Transducing; D001120:Arginine; D028884:Karyopherins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D011484:Protein-Arginine N-Methyltransferases; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D000097606:Exportin 1 Protein; C000627127:NRIP1 protein, human; C099988:PRMT1 protein, human