Deciphering Post-Translational Modifications: Their Role in Cellular Signaling and Metabolic Pathways

Abstract

Post-translational modifications (PTMs) are another control mechanism which has been shown to be a major form of cellular regulation and an added layer of structural and functional diversity to proteins beyond the information that the cellular genome provides. PTMs are molecular switches that help to regulate the activity, stability, localization, and interactions of proteins by converting molecule chemical states with phosphorylation, ubiquitination, acetylation, glycosylation, and methylation. It is this complexity that allows cells to integrate environmental signals, assemble metabolic processes and dynamically control pathways needed to survive and adapt. The importance of PTMs in cellular signaling and metabolism is very evident in their role in DNA repair, apoptosis, immune response and energy metabolism. PTMs disruption has also been widely recognized as a leading cause of diseases, including cancer, diabetes and neurodegenerative conditions. However, recent developments in mass spectrometry, proteomics and bio informatics have significantly expanded our understanding of PTMs to the point that it is now possible to map both modification site and network on a large scale. A comprehensive description of the application of PTMs to cellular processes and metabolic pathways is provided in the paper. It talks about classical and novel phosphorylation and ubiquitination and SUMOylation and ADPribosylation. The crosstalk of PTMs and how they might be exploited to optimally tune biological processes by making decisions at multiple sites on the same protein, which may either interact synergistically or antagonistically, is discussed. It also talks about advances in high-throughput proteomics methodology and computational modeling that are used to decipher the complexity of PTM. The other more informative PTM network applications that are not directly related to pure biology also have therapeutic applications as they are a form of differential manipulation of the PTMs in human disease.