Lysine methylation of nuclear co-repressor receptor interacting protein 140

Mostaqul Huq, Sung Gil Ha, Helene Barcelona, Li Na Wei

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Receptor interacting protein 140 (RIP140) undergoes extensive post-translational modifications (PTMs), including phosphorylation, acetylation, arginine methylation, and pyridoxylation. PTMs affect its subcellular distribution, protein-protein interaction, and biological activity in adipocyte differentiation. Arginine methylation on Arg 240, Arg 650, and Arg 948 suppresses the repressive activity of RIP140. Here, we find that endogenous RIP140 in differentiated 3T3-L1 cells is also modified by lysine methylation. Three lysine residues, Lys 591, Lys 653, and Lys 757, are mapped as potential methylation sites by mass spectrometry. Site-directed mutagenesis study shows that lysine methylation enhances its gene repressive activity. Mutation of lysine methylation sites enhances arginine methylation, while mutation on arginine methylation sites has little effect on its lysine methylation, suggesting a relationship between lysine methylation and arginine methylation. Kinetic analysis of PTMs of endogenous RIP140 in differentiated 3T3-L1 cells demonstrates sequential modifications on RIP140, initiated from constitutive lysine methylation, followed by increased arginine methylation later in differentiation. This study reveals a potential hierarchy of modifications, at least for lysine and arginine methylation, which bidirectionally regulate the functionality of a nonhistone protein.

Original languageEnglish (US)
Pages (from-to)1156-1167
Number of pages12
JournalJournal of Proteome Research
Volume8
Issue number3
DOIs
StatePublished - Mar 6 2009

Keywords

  • Adipocytes differentiation
  • Lysine methylation
  • Mass spectrometry
  • Post-translational modification
  • Receptor interacting protein 140

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