All hands on DEK: structural insights into a unique histone modifier and chromatin remodeler

DEK is a chromatin-associated, DNA-binding protein with unique properties that place it in its own protein class. First discovered in 1992 as a fusion protein in acute myeloid leukemia, DEK gained further attention in the mid-2000s as a growing number of studies identified its connections to chromatin architecture and subsequent impact on pathologies such as cancer and autoimmune diseases. Current evidence indicates that DEK can alter the topology of nucleic acids in a variety of biological processes, including DNA replication, DNA repair, chromatin organization, epigenetic modification, transcription, and mRNA splicing. Interestingly, DEK is highly evolutionarily conserved among higher eukaryotes, and this, combined with its involvement in such a diverse array of processes, highlights its biological significance. Interest in DEK is further driven by its status as a potent oncogene, as it is transcriptionally upregulated in most solid tumors tested to date, with high DEK expression correlating with poor survival and more aggressive tumors. Recently, advances in cryogenic electron microscopy have made it possible to visualize the structural basis of DEK-nucleosome interactions, providing concrete mechanistic insights into how DEK influences gene regulation and transcription. These findings clarify prior observations and open new avenues for exploring the biological and clinical relevance of DEK.