CI-994, HDAC inhibitor. Cell-permeable.

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

HDAC1 HDAC2 and HDAC3 also known collectively as Class I histone deacetylases function as critical enzymes in chromatin remodeling by removing acetyl groups from lysine residues on histone and non-histone proteins. HDAC1 has a molecular mass of approximately 55 kDa HDAC2 is slightly smaller at around 53 kDa and HDAC3 similarly weighs around 49 kDa. These deacetylases are ubiquitously expressed in various tissues where they play roles in regulating gene expression and influencing cell cycle progression apoptosis and differentiation processes.

Biological function summary

These histone deacetylases contribute to gene silencing and transcriptional repression. HDAC1 HDAC2 and HDAC3 often form multi-protein complexes such as the Sin3 NuRD and CoREST complexes. These complexes interact with co-repressor proteins allowing the HDACs to modulate the acetylation status of histones and therefore repress transcription. The ability of HDACs to alter chromatin structure and gene expression affects numerous cellular functions including growth and metabolic regulation.

Pathways

The activity of HDAC1 HDAC2 and HDAC3 is integral to the regulation of important regulatory pathways such as the Wnt signaling and p53 pathways. Through these pathways they interact with transcription factors and other regulatory proteins. In the Wnt signaling pathway these HDACs can modify the transcriptional activity of beta-catenin and associated gene targets. Moreover their involvement in the p53 pathway aids in regulating cell cycle arrest and apoptosis impacting vital cellular responses to DNA damage in collaboration with proteins like MDM2 and p21.

Dysregulation of HDAC1 HDAC2 and HDAC3 is linked to cancer and neurodegenerative diseases. In various cancers aberrant expression of these HDACs can lead to unregulated cell growth and survival due to altered gene expression profiles. For neurodegenerative disorders such as Alzheimer's disease altered HDAC activity can influence the expression of genes involved in inflammation and synaptic function. Proteins such as amyloid precursor protein (APP) and tau may be affected tying HDAC dysregulation to pathological changes observed in neurodegeneration.