Post-translational acetylation of proteins has recently been reported as a common modification to cellular proteins.  Lysine deacetylases (KDACs) are responsible for reversing this modification.  KDACs are an important potential protein target to control the development and progression of many diseases, including several cancers.  However, the cellular substrates of the non-histone KDACs are largely unknown.  In addition, some KDACs have very low activity in standard assays.  Our goal is to obtain information regarding the biochemical recognition of proteins by KDACs.  We have developed a system to screen potential substrates using a scaffold protein that presents a variable region to the KDACs.  We report optimized conditions for determining the activity of the scaffold protein as a proxy for ensuring that introduced substrate sequence does not perturb the scaffold structure.  In addition, we report on progress toward understanding the regulation of the activity of KDACs by small molecules.  These improvements to components of the KDAC activity screens will permit novel approaches to understand the specificity of KDACs.

Enhancing methods for lysine deacetylase substrate identification

247th National Meeting (2014)

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