Kinetic Characterization of Human Histone Deacetylase 8 With Medium-Chain Fatty Acyl Lysine.
Harrison YooGregory A PolsinelliPublished in: Epigenetics insights (2021)
Histone deacetylases (HDACs) catalyze the removal of Ɛ-acetyl-lysine residues of histones via hydrolysis. Removal of acetyl groups results in condensation of chromatin structure and alteration of gene expression by repression. HDACs are considered targets for the treatment of cancer due to their role in regulating transcription. HDAC8 inhibition may be an important anti-proliferative factor for histone deacetylase inhibitors on cancer cells and may give rise to the progression of apoptosis. HDAC8 activity was analyzed with various peptides where the target lysine is modified with medium-chain fatty acyl group. Kinetic data were determined for each p53 peptide substrate. The results suggest that there was HDAC8 deacetylase activity on peptide substrate as well as deacylase activity with acylated peptide substrate variants. HDAC8 inhibition by hexanoic and decanoic acid was also examined. The K i for hexanoic and decanoic acid were determined to be 2.35 ± 0.341 and 4.48 ± 0.221 mM, respectively.
Keyphrases
- histone deacetylase
- gene expression
- amino acid
- dna methylation
- fatty acid
- transcription factor
- endothelial cells
- oxidative stress
- cell death
- genome wide
- endoplasmic reticulum stress
- squamous cell carcinoma
- electronic health record
- young adults
- machine learning
- big data
- artificial intelligence
- cell cycle arrest
- combination therapy
- deep learning