Histone deacetylase 5 (HDAC5) (HDAC5)

Histone deacetylase 5 (HDAC5) is a Class IIa histone deacetylase that regulates gene expression by removing acetyl groups from lysine residues on histones and various non-histone proteins (UniProt). Unlike Class I HDACs, HDAC5 can shuttle between the nucleus and cytoplasm, a process tightly regulated by phosphorylation and interaction with 14-3-3 proteins (PubMed). In the nucleus, it acts as a transcriptional corepressor for factors such as MEF2, playing a vital role in muscle differentiation, cardiac remodeling, and neuronal survival (Wikipedia). HDAC5 is frequently overexpressed in several cancers, including breast and hepatocellular carcinoma, where it promotes cell proliferation, epithelial-mesenchymal transition, and resistance to chemotherapy (NIH). It also interacts with other epigenetic enzymes like LSD1 to maintain the stability of oncogenic signaling complexes (PubMed). Therapeutic strategies targeting HDAC5 involve small-molecule inhibitors that block its zinc-dependent catalytic activity, leading to chromatin relaxation and the reactivation of tumor suppressor genes (PubChem). However, the clinical utility of current HDAC inhibitors is often hampered by systemic toxicities such as myelosuppression and cardiotoxicity, necessitating the development of more isoform-selective inhibitors (NIH).

Other names

HD5NY-CO-9Antigen NY-CO-9Lysine deacetylase 5

Inhibition of the zinc-dependent catalytic domain, leading to histone hyperacetylation, chromatin relaxation, and the reactivation of tumor suppressor genes.