Using the Conserved Hexapeptide in HOX Proteins as an Antagonist of HOX/PBX Interactions

The HOX and PBX genes encode transcription factors that have key roles in development and cancer, both independently and as a heterodimer within a complex of proteins that recognizes specific sequences in DNA and can both activate and repress transcription of target genes. Due to functional redundancy amongst HOX proteins, knock down or knock out studies of individual genes often do not result in an altered phenotype. An alternative approach is to target the interaction between HOX and PBX proteins, which is dependent on a conserved hexapeptide region within HOX. To this end, several peptides have been developed based on the hexapeptide sequence which act as competitive antagonists of HOX/PBX binding, including HXR9 and HTL001. Here, we review the methodology that has been used in these studies, including peptide syntheses, cell culture, assays, and mouse models.