Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Abstract

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

Chemical proteomic profiling of protein dopaminylation in colorectal cancer cells

“…1 Due to their fundamental functions in cell signaling, 2,3 to target the dynamics (including the installation and removal) of protein PTMs becomes a considerable therapeutic strategy for human disease treatment. 4 In general, the dynamics of protein PTMs are regulated by “writer” and “eraser” enzymes. 5 In the past years, we focused on non-canonical protein PTMs that do not require writers (such as non-enzymatic glycation), 6–9 or in which the installation and removal are regulated by a single enzyme (such as monoaminylation).…”

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

“…Alternatively, phospho-signals, serving as the first wave of response to intracellular and extracellular changes, extensively exist during the EMT process [65,66]. For example, phosphorylation of SNAIL [67], GSK3β [68], and EGFR [69] contributes to the regulation of EMT.…”

“…Mg deficiency is well known to cause inflammation by disturbing the coordination of the innate immune system and the adaptive immune response[14], leading to rapid loss of cell adhesion molecules[46−48]. Alternatively, phospho-signals, serving as the first wave of response to intracellular and extracellular changes, extensively exist during the EMT process[65, 66]. For example, phosphorylation of SNAIL[67], GSK3β[68], and EGFR[69] contributes to the regulation of EMT.…”

Remodeling of the protein ubiquitylation landscape in the aging vertebrate brain

“…PTMs modulate the function of proteins by regulating their localization, interactions, stability, and turnover, thereby influencing protein homeostasis (proteostasis) (Zhong et al, 2023). Loss of proteostasis is a hallmark of aging (Santra et al, 2019;C.…”