The Function and related Diseases of Protein Crotonylation

Abstract

Crotonylation is a kind of newly discovered acylation modification. Thousands of crotonylation sites have been identified in histone and non-histone proteins over the past decade. As a modification closely related to acetylation, crotonylation was reported to share many universal enzymes with acetylation. Crotonylated proteins have important roles in the regulation of various biological processes, such as gene expression, process of spermatogenesis, cell cycle, and also in the pathogenesis of different diseases, which range from depression to cancer. In this review, we summarize the research processes of crotonylation and discuss the advances of regulation mechanism of both histone and non-histone proteins crotonylation in difference physiological processes. Also, we focus on the alteration of the crotonylation under certain pathological conditions and its role in the pathogenesis of each disease.

Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis

“…Crotonylation is differentially regulated by two factors: modification enzymes and small-molecule acyl-coenzymes (crotonyl-CoA) ( Fang et al, 2021 ). These include p300/CBP as crotonyltransferases and class I histone deacetylases, HDAC1, HDAC2, and HDAC3 as decrotonylase enzymes ( Wang et al, 2021 ). The HDAC2 level in the brain was slightly down-regulated in the following of SB treatment ( Supplementary Figures S7D,E ), which was not correlated with significantly up-regulated butyric acid level in the brain ( Figure 6B ).…”

“…Metabolism and gene expression regulate each other, and epigenetic modification usually acts as a molecular link between the two fundamental processes ( Ren et al, 2021 ). Histone modifications, such as acetylation and crotonylation, are closely related to transcriptional regulation, and crotonylation is a more potent transcriptional activator than acetylation ( Liu et al, 2017 ; Ratajczak et al, 2019 ; Wang et al, 2021 ). Of note, some studies have shown that crotonylation is relatively enriched near the transcription start sites of genes involved in various metabolic processes in pluripotent stem cells ( Fang et al, 2021 ).…”

Lactylation may be a Novel Posttranslational Modification in Inflammation in Neonatal Hypoxic-Ischemic Encephalopathy

“…Classic posttranslational modifications, such as acetylation, malonylation, and succinylation, disturb the spatial structure of proteins to control a variety of physiological and biochemical activities in cells ( Tarazona and Pourquie, 2020 ; Gupta et al, 2021 ). Propionylation ( Chen et al, 2007 ), butyrylation ( Zhang et al, 2009 ), crotonylation ( Wang et al, 2021 ), malonylation ( Xie et al, 2012 ), succinylation ( Mu et al, 2021 ), glutarylation ( Bao et al, 2019 ), 2-hydroxyisobutyrylation ( Dai et al, 2014 ), hydroxybutyrylation ( Xie et al, 2016 ), and lactonylation ( Zhang et al, 2019 ) are nine novel types of histone lysine (K) acylation that were detected by high-resolution mass spectrometry-based proteomics analysis. These novel histone modifications differ from histone lysine acylation in terms of hydrocarbon chain length, hydrophobicity, and charge and drastically increase the diversity of histone modifications.…”

Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer

“…Lysine crotonylation (Kcr) was first discovered in 2011 [ 190 ]. At present, a variety of histone and non-histone lysine residues have been found to undergo crotonylation [ 21 , 191 ]. Notably, the majority of histone Kcr sites identified thus far are located in transcriptional initiation sites (TSSs) and enhancer regions, indicating that histone Kcr may play an important role in gene regulation [ 190 ].…”