The GCN5: its biological functions and therapeutic potentials

Clin Sci (Lond). 2021 Jan 15;135(1):231-257. doi: 10.1042/CS20200986.

Abstract

General control non-depressible 5 (GCN5) or lysine acetyltransferase 2A (KAT2A) is one of the most highly studied histone acetyltransferases. It acts as both histone acetyltransferase (HAT) and lysine acetyltransferase (KAT). As an HAT it plays a pivotal role in the epigenetic landscape and chromatin modification. Besides, GCN5 regulates a wide range of biological events such as gene regulation, cellular proliferation, metabolism and inflammation. Imbalance in the GCN5 activity has been reported in many disorders such as cancer, metabolic disorders, autoimmune disorders and neurological disorders. Therefore, unravelling the role of GCN5 in different diseases progression is a prerequisite for both understanding and developing novel therapeutic agents of these diseases. In this review, we have discussed the structural features, the biological function of GCN5 and the mechanical link with the diseases associated with its imbalance. Moreover, the present GCN5 modulators and their limitations will be presented in a medicinal chemistry perspective.

Keywords: GCN5; Histone Acetyltransferase; Therapeutic implications; Transcriptional Regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Antineoplastic Agents / pharmacology
  • Chromatin Assembly and Disassembly* / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic* / drug effects
  • Histone Acetyltransferases / antagonists & inhibitors
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Histones / metabolism*
  • Humans
  • Lysine
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Protein Domains
  • Protein Processing, Post-Translational
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histones
  • Histone Acetyltransferases
  • KAT2A protein, human
  • Lysine