Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease

• Published in: The FEBS journal 2023-06, Vol.290 (11), p.2805-2832
• Main Authors: Wang, Yizhuo, Abrol, Rishika, Mak, Jeffrey Y. W., Das Gupta, Kaustav, Ramnath, Divya, Karunakaran, Denuja, Fairlie, David P., Sweet, Matthew J.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Biological activity; Cell differentiation; Cell proliferation; Cell survival; class IIa HDAC; Differentiation (biology); Disease; Endothelium; Epithelium; Gene expression; gene regulation; HDAC protein; HDAC7; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylase Inhibitors - therapeutic use; Histone Deacetylases - metabolism; Histones; Humans; Immune system; immunometabolism; In vivo methods and tests; Inflammation; Lysine; macrophage; Metabolism; Molecular modelling; Neoplasms; Osteoclasts; Proteins; Signal Transduction - genetics; State‐of‐the‐Art Review; State‐of‐the‐Art Reviews
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.16437

Histone deacetylases (HDACs) catalyse removal of acetyl groups from lysine residues on both histone and non‐histone proteins to control numerous cellular processes. Of the 11 zinc‐dependent classical HDACs, HDAC4, 5, 7 and 9 are class IIa HDAC enzymes that regulate cellular and developmental processes through both enzymatic and non‐enzymatic mechanisms. Over the last two decades, HDAC7 has been associated with key roles in numerous physiological and pathological processes. Molecular, cellular, in vivo and disease association studies have revealed that HDAC7 acts through multiple mechanisms to control biological processes in immune cells, osteoclasts, muscle, the endothelium and epithelium. This HDAC protein regulates gene expression, cell proliferation, cell differentiation and cell survival and consequently controls development, angiogenesis, immune functions, inflammation and metabolism. This review focuses on the cell biology of HDAC7, including the regulation of its cellular localisation and molecular mechanisms of action, as well as its associative and causal links with cancer and inflammatory, metabolic and fibrotic diseases. We also review the development status of small molecule inhibitors targeting HDAC7 and their potential for intervention in different disease contexts. Histone deacetylase 7 (HDAC7) is a lysine deacetylase and scaffolding protein that regulates numerous cellular and developmental processes via its multifaceted roles in signal transduction and gene regulation. This review summarises the many functions of HDAC7 in different cell types during homeostasis, our current understanding of associations between dysregulated HDAC7 expression and/or function and human disease, and the developmental status of small molecule HDAC7 inhibitors.