Histone deacetylase 8 (HDAC8) (HDAC8)

Histone deacetylase 8 (HDAC8) is a member of the Class I zinc-dependent histone deacetylases, uniquely characterized by its X-linked gene location and its ability to function independently of large co-repressor complexes [1, 16]. Unlike other Class I HDACs, HDAC8 is found in both the nucleus and cytoplasm and plays a critical role in deacylating non-histone substrates, most notably the cohesin complex subunit SMC3, which is essential for sister chromatid cohesion and recycling [1, 12, 14]. In oncology, HDAC8 is frequently overexpressed in high-risk neuroblastoma and T-cell lymphomas, where it promotes cell survival and inhibits differentiation, making it a significant therapeutic target [1, 3]. Conversely, loss-of-function mutations in the HDAC8 gene are a known cause of Cornelia de Lange Syndrome (CdLS), a developmental disorder characterized by intellectual disability and physical abnormalities [8, 11]. Pharmacological targeting of HDAC8 involves both pan-HDAC inhibitors like Vorinostat and isoform-selective inhibitors such as PCI-34051, which aim to induce apoptosis and cell cycle arrest in malignant cells [1, 20]. Ongoing research also explores HDAC8's involvement in viral infections, smooth muscle contraction, and various fibrotic conditions [1, 4, 12].

Other names

HD8RPD3WTSCDA07MRXS6Protein deacetylase HDAC8Protein decrotonylase HDAC8

Inhibition of histone deacetylase activity, leading to hyperacetylation of histones and non-histone proteins (such as SMC3 and p53), which results in cell cycle arrest, induction of apoptosis, and modulation of gene expression patterns [1, 3, 5, 10].