The Role of Post-Translational Acetylation and Deacetylation of Signaling Proteins and Transcription Factors after Cerebral Ischemia: Facts and Hypotheses

Svetlana Demyanenko,Svetlana Sharifulina

doi:10.3390/ijms22157947

Abstract

Histone deacetylase (HDAC) and histone acetyltransferase (HAT) regulate transcription and the most important functions of cells by acetylating/deacetylating histones and non-histone proteins. These proteins are involved in cell survival and death, replication, DNA repair, the cell cycle, and cell responses to stress and aging. HDAC/HAT balance in cells affects gene expression and cell signaling. There are very few studies on the effects of stroke on non-histone protein acetylation/deacetylation in brain cells. HDAC inhibitors have been shown to be effective in protecting the brain from ischemic damage. However, the role of different HDAC isoforms in the survival and death of brain cells after stroke is still controversial. HAT/HDAC activity depends on the acetylation site and the acetylation/deacetylation of the main proteins (c-Myc, E2F1, p53, ERK1/2, Akt) considered in this review, that are involved in the regulation of cell fate decisions. Our review aims to analyze the possible role of the acetylation/deacetylation of transcription factors and signaling proteins involved in the regulation of survival and death in cerebral ischemia.

Highlights

Acetylation of histones and non-histone proteins modulates gene expression and signaling in cells
histone acetyltransferase (HAT)/Histone deacetylase (HDAC) activity depends on the acetylation site and the acetylation/deacetylation of the main proteins (c-Myc, E2F1, p53, ERK1/2, Akt) considered in this review, that are involved in the regulation of cell fate decisions
It has been shown that an inhibition of HDAC1 and HDAC6 downregulated the expression of phospho-ERK1 in human head and neck squamous cell carcinoma cells [118]

Summary

Introduction

Acetylation of histones and non-histone proteins modulates gene expression and signaling in cells. The study of non-histone protein acetylation/deacetylation began after the success of the clinical use of histone deacetylase inhibitors (HDACs) in the treatment of various forms of cancer and was driven by the search for the causes of cytotoxicity of nonselective HDAC inhibitors (HDACi) [2]. The number of identified proteins in which activity is regulated by acetylation/deacetylation to date is certainly lower than the actual amount represented by acetylome in vivo. There are very few studies on the non-histone protein acetylation/deacetylation in brain cells, and there is apparently no data on these processes in stroke. Our review aims to analyze the possible role of acetylation/deacetylation of transcription factors and signaling proteins involved in the regulation of apoptosis in ischemia

Protein Acetylation and Deacetylation Enzymes

Histone Deacetylases

Post-Translational Modifications of HDACs

Biological Activity of HDAC Inhibitors

Non-Histone Substrates of HAT and HDAC

13. Conclusions and Outlook