Protein acylation: mechanisms, biological functions and therapeutic targets

Abstract

Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein–protein interactions and protein–DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.

New Histone Lysine Acylation Biomarkers and Their Roles in Epigenetic Regulation

“…For example, SIRT2 was reported as an ‘eraser’ to remove acetyl, crotonyl, methacrylyl, and benzoyl marks on histones as well as non‐histone proteins (Bao et al., 2014; Bhaskar et al., 2020; Delaney et al., 2021; Huang et al., 2018; Ntorla & Burgoyne, 2021; Serrano et al., 2013; Yi et al., 2021). Some studies have found that metabolic enzymes are involved in the pathogenesis of diseases by targeting more than one modification (Shang et al., 2022). Therefore, profiling dynamic changes of different modifications and elucidating how they compete with regulatory enzymes for downstream functionality is important to understand the underlying mechanisms of diseases.…”

Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments

“…CoA also mediates the covalent transfer of other acyl moieties to proteins for the dynamic modulation of their activity. Several acyl-CoA metabolites, including succinyl-CoA, propionyl-CoA, crotonyl-CoA, and palmitoyl-CoA, can be covalently attached to the side chains of lysines of proteins in different cellular compartments [ 36 ]. As for acetylation, the acylation of proteins has a role in regulating cellular processes, such as gene expression and chromatin accessibility, metabolic regulation, subcellular targeting, protein–membrane interactions, protein stability, and folding [ 37 ].…”

Localization and Quantification of Post-Translational Modifications of Proteins Using Electron Activated Dissociation Fragmentation on a Fast-Acquisition Time-of-Flight Mass Spectrometer

“…Phosphorylation primarily modifies serine residues followed by threonine and tyrosine residues, in eukaryotes, but can also be present on histidine and aspartic acid residues in prokaryotes, and these modifications can lead to strong structural rearrangements . Changes in PTM profiles are associated with dysregulated biological mechanisms and diseases, such as metabolism disorder, inflammation, neurodegenerative diseases, cancer, and cardiovascular disease. − Highly specific kinase inhibitors, for example, provide popular therapeutic intervention mechanisms for diseases. − …”