Post-Translational Modifications of Nuclear Co-repressor RIP140: A Therapeutic Target for Metabolic Diseases

Most proteins undergo post-translational modification (PTM), which is known to play roles in normal physiological processes and the progression of many diseases. In this review, we summarized and discussed the mass spectrometry (MS)-based studies of various PTMs of nuclear co-repressor, receptor interacting protein 140 (RIP140), as well as the significance of these PTMs in modulating the biological activities of RIP140, specifically in adipocytes. Comprehensive analyses of RIP140 by MS identified specific sites of PTMs on RIP140, including that of phosphorylation, acetylation, pyridoxylation, and protein arginine methylation. Studies of these PTMs revealed their combinatorial effects on the activities of RIP140 with respect to the regulation of hormone target genes and fat accumulation in adipocytes. These proteomic studies have presented evidence for the biological significance of specific PTMs of RIP140, and uncovered nutritional and physiological factors that trigger these PTMs in adipocytes.. This could provide insights into potential, new therapeutic targets for diseases concerning adipocytes such as metabolic disorders.