Mostaqul Huq M D, Gupta Pawan, Wei Li-Na
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN55455, USA.
Curr Med Chem. 2008;15(4):386-92. doi: 10.2174/092986708783497382.
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.
大多数蛋白质会经历翻译后修饰（PTM），已知其在正常生理过程和许多疾病的发展中发挥作用。在本综述中，我们总结并讨论了基于质谱（MS）对核共抑制因子、受体相互作用蛋白140（RIP140）各种翻译后修饰的研究，以及这些修饰在调节RIP140生物学活性中的意义，特别是在脂肪细胞中的意义。通过质谱对RIP140进行的综合分析确定了RIP140上翻译后修饰的特定位点，包括磷酸化、乙酰化、吡哆醛化和蛋白质精氨酸甲基化位点。对这些翻译后修饰的研究揭示了它们在调节激素靶基因和脂肪细胞中脂肪积累方面对RIP140活性的组合效应。这些蛋白质组学研究为RIP140特定翻译后修饰的生物学意义提供了证据，并揭示了在脂肪细胞中触发这些修饰的营养和生理因素。这可能为诸如代谢紊乱等与脂肪细胞有关的疾病提供潜在的新治疗靶点的见解。
