Application

Useful for the study of enzyme kinetics, screening inhibitors, and selectivity profiling.

Biochem/physiol Actions

HDAC8 (histone deacetylase 8) is a regulator of cohesion protein and is essential for recycling of cohesin during cell cycle. This protein functions on both histone and non-histone substrates, and produces free lysine and acetate by catalyzing the hydrolysis of acetyllysine side chain. Till date, 17 missense mutations in this gene have been identified in patients with Cornelia de Lange Syndrome (CdLS) spectrum disorders, where these mutations have led to partial or complete loss of deacetylase function. This protein is linked with malignant types of neuroblastoma, and its expression in patients with metastatic melanoma is linked with increased survival in the same. Studies show that HDAC8 can abnormally deacetylate and inactivate p53 protein, thus, facilitating leukemia stem cells (LSCs) transformation and maintenance. LSCs are essential for promoting and sustaining acute myeloid leukemia (AML), and HDAC8 inactivation results in normal p53 function in inv(16)(+) AML CD34(+) cells.

General description

HDAC8 (histone deacetylase 8) is a class I Zn²⁺-dependent SMC3 (structural maintenance of chromosomes 3) deacetylase. It is the human ortholog of the yeast Zn²⁺-dependent deacetylase Hos1.

Physical form

Formulated in 25 mM Tris-HCl, pH 8.0, 138 mM NaCl, 0.05% Tween-20 and 10% glycerol.

Preparation Note

Thaw on ice. Upon first thaw, briefly spin tube containing enzyme to recover full content of the tube. Aliquot enzyme into single use aliquots. Store remaining undiluted enzyme in aliquots at -70°C. Note: Enzyme is very sensitive to freeze/thaw cycles.

Unit Definition

One unit is defined as the amount of enzyme required to deacetylate 1 pmol of substrate/min at 37°C.