Protein acetylation and deacetylation: An important regulatory modification in gene transcription (Review)

Abstract

Cells primarily rely on proteins to perform the majority of their physiological functions, and the function of proteins is regulated by post-translational modifications (PTMs). The acetylation of proteins is a dynamic and highly specific PTM, which has an important influence on the functions of proteins, such as gene transcription and signal transduction. The acetylation of proteins is primarily dependent on lysine acetyltransferases and lysine deacetylases. In recent years, due to the widespread use of mass spectrometry and the emergence of new technologies, such as protein chips, studies on protein acetylation have been further developed. Compared with histone acetylation, acetylation of non-histone proteins has gradually become the focus of research due to its important regulatory mechanisms and wide range of applications. The discovery of specific protein acetylation sites using bioinformatic tools can greatly aid the understanding of the underlying mechanisms of protein acetylation involved in related physiological and pathological processes.

Keywords: acetylation; deacetylation; lysine acetyltransferase; lysine deacetylases; non-histone protein acetylation.

Figure 1

Biological processes regulated by acetyltransferase GCN5 and p300/CBP. GCN5 acetylates TFEB at K274 and K279, hindering the binding of TFEB to its target gene promoters CLCN7, GLA and CTSD. This process inhibits the biogenesis of lysosomes and aggregation of autophagosomes. In addition, the acetylation of E2F1 at K117, K120 and K125 by acetyltransferase p300/CBP creates a binding motif at the BD of the p300/CBP protein to attract more p300/CBP with the help of RB tumor-suppressor protein. Subsequently, the recruitment of p300/CBP induces the acetylation of H3K18 and H3K56, and then facilitates the binding of chromatin-modifying enzymes and repair factors for DNA double-strand breaks. GCN5, general control of amino acid synthesis protein 5; CBP, CREB-binding protein; TFEB, transcription factor EB; CLCN7, chloride voltage-gated channel 7; GLA, galactosidase α; CTSD, cathepsin D; E2F1, E2F transcription factor 1; BD, bromodomains; RB, retinoblastoma.

Figure 2

Acetylation and deacetylation associated with EMT. Snail, a zinc finger protein, comprises a C-terminal zinc finger domain and an N-terminal SNAG domain. The C-terminal zinc finger domain recognizes the E-box sequence in the promoter region of E-cadherin. The SNAG domain associates with HDAC1/2 and corepressor mSin3A, and then recruits the repressor complex to the E-cadherin promoter, where HDAC1/2 deacetylate histone H3 and H4, inhibiting the expression of E-cadherin and promoting the process of EMT. Human c-Jun is a transcriptional regulator of JUN proto-oncogene. It is reported that the downregulation of HDAC3 expression can increase the acetylation of c-Jun and may lead to the degradation of c-Jun, which ultimately increases the expression of E-cadherin and decreases the expression of snail, thus inhibiting the process of EMT. EMT, epithelial-mesenchymal transition; Snail, zinc finger protein SNAI1; HDAC, histone deacetylase.

Figure 3

GCN5 enhances the osteogenic differentiation of PDLSCs. GCN5 is a type of KAT that catalyzes the acetylation of H3K9 and H3K14, and promotes the expression of DKK1. As a secreted protein, DKK1 can form trimers with LRP5/6 and Kremen1/2, inhibit the Wnt/β-catenin pathway, and activate the Wnt/Ca²⁺ pathway. The decrease of β-catenin and the increase of Ca²⁺ ultimately facilitates osteogenic differentiation of PDLSCs. GCN5, general control of amino acid synthesis protein 5; PDLSCs, periodontal ligament stem cells; KATs, lysine acetyltransferases; DKK1, dickkopf-related protein 1; LRP5/6, LDL-receptor-related protein 5/6.