Small changes huge impact: the role of protein posttranslational modifications in cellular homeostasis and disease

Abstract

Posttranslational modifications (PTMs) modulate protein function in most eukaryotes and have a ubiquitous role in diverse range of cellular functions. Identification, characterization, and mapping of these modifications to specific amino acid residues on proteins are critical towards understanding their functional significance in a biological context. The interpretation of proteome data obtained from the high-throughput methods cannot be deciphered unambiguously without a priori knowledge of protein modifications. An in-depth understanding of protein PTMs is important not only for gaining a perception of a wide array of cellular functions but also towards developing drug therapies for many life-threatening diseases like cancer and neurodegenerative disorders. Many of the protein modifications like ubiquitination play a decisive role in various drug response(s) and eventually in disease prognosis. Thus, many commonly observed PTMs are routinely tracked as disease markers while many others are used as molecular targets for developing target-specific therapies. In this paper, we summarize some of the major, well-studied protein alterations and highlight their importance in various chronic diseases and normal development. In addition, other promising minor modifications such as SUMOylation, observed to impact cellular dynamics as well as disease pathology, are mentioned briefly.

Figure 1

Post-translational modifications for p53, a tumor-suppressor protein, responsible for maintaining the genomic stability in a cell. The figure illustrates various posttranslational modifications that are frequently observed in p53 with varied functional implications in normal and/or diseased condition. The amino acid residues that most often undergo the respective modifications in a given context have been highlighted. For details of posttranslational alterations in p53 refer to [–127].