Class IIb histone deacetylase (Class IIb HDACs)

Class IIb histone deacetylases (HDACs) are a distinct subgroup of the zinc-dependent HDAC family, consisting of HDAC6 and HDAC10 (UniProt P56524, Q969S8). Unlike other HDAC classes that primarily target nuclear histones to regulate gene expression, Class IIb enzymes are predominantly localized in the cytoplasm and deacetylate a wide array of non-histone proteins (PMID: 22013090). HDAC6 is unique for having two tandem catalytic domains and a C-terminal zinc-finger ubiquitin-binding domain, which facilitates the transport of misfolded proteins to aggresomes for degradation (PMID: 28137777). HDAC10 has been identified as a polyamine deacetylase that plays a significant role in promoting autophagy and cell survival, particularly in advanced cancers like neuroblastoma (PMID: 26183060). These enzymes are implicated in various pathologies, including oncology, where they support tumor cell proliferation and metastasis, and neurodegenerative diseases, where they affect axonal transport and protein aggregation (PMID: 30635457). Therapeutic strategies often focus on selective inhibition of HDAC6 to avoid the systemic toxicities associated with pan-HDAC inhibitors, with several candidates like ricolinostat undergoing clinical evaluation for multiple myeloma and solid tumors (PubChem CID 49850319).

Other names

HDAC6HDAC10Histone deacetylase 6Histone deacetylase 10Cytoplasmic HDACs

Inhibition of the catalytic deacetylase activity of HDAC6 and HDAC10, leading to the hyperacetylation of non-histone substrates such as alpha-tubulin, Hsp90, and cortactin, which disrupts cellular processes including protein trafficking, aggresome formation, and autophagic flux (PMID: 28137777, PMID: 26183060).