The DEK protein has been implicated in the pathogenesis of several cancers as well as in autoimmune disease, although its biological function remains unclear. DEK has been associated with three separate but potentially related functions including site-specific DNA binding and transcription regulation, alterations in the topology of DNA and chromatin, and RNA processing events. One mechanism by which a single polypeptide can exhibit different functional properties is through posttranslational modifications. Indeed, DEK is both differentially phosphorylated and acetylated in vivo and these modifications alter the cellular phenotype of DEK. Importantly, when DEK is acetylated, it moves from being a diffuse nuclear protein to one that is concentrated in nuclear speckles. Therefore, investigation into the mechanism and cellular function of DEK acetylation may provide critical insight into how DEK is able to function in diverse steps in the gene expression pathway. Specifically, reagents that affect the dynamic equilibrium of the in vivo phosphorylation and acetylation state will be used to determine the role of posttranslational modifications on the DNA binding affinity of DEK. Furthermore, identification of the specific lysine residues that are conditionally acetylated in DEK by mass spectroscopy should facilitate the elucidation of residues that are responsible for the sub-nuclear localization of DEK and those that may contribute to DNA-binding or the known association with other cellular factors. Dysregulation of posttranslational modifications of DEK may ultimately be related to its role in disease and so understanding this level of regulation could lead to therapeutic advances.
