Protein-protein and protein-chromatin interactions of LEDGF/p75 as novel drug targets

Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional co-activator, plays an important role in tethering protein complexes to the chromatin. Through this tethering function LEDGF/p75 is implicated in a diverse set of human diseases including HIV infection and mixed lineage leukemia, an aggressive form of cancer with poor prognosis. Here we provide an overview of recent progress in resolving protein-protein and protein-chromatin interaction mechanisms of LEDGF/p75. This review will focus on two well-characterized domains, the PWWP domain and the integrase binding domain (IBD). The PWWP domain interacts with methylated lysine 36 in histone H3, a marker of actively transcribed genes. The IBD interacts with the IBD binding motif, available in cellular binding partners of LEDGF/p75. Each domain forms an interesting new target for drug discovery.