Pre-B-cell leukemia homeobox protein (PBX) (PBX)

The Pre-B-cell leukemia homeobox (PBX) proteins are a family of TALE-class homeodomain transcription factors, including PBX1, PBX2, and PBX3, that serve as essential co-factors for HOX proteins. The interaction between PBX and HOX proteins is mediated by a conserved hexapeptide motif (often containing a YPWM sequence) found in HOX proteins, which inserts into a specific hydrophobic binding pocket on the PBX homeodomain. This HOX-PBX dimerization is critical for increasing the DNA-binding affinity and specificity of HOX proteins, allowing them to regulate complex gene expression programs during embryonic development and cell differentiation. In many adult malignancies, such as leukemia and various solid tumors, the dysregulation or overexpression of HOX and PBX proteins drives oncogenic pathways and promotes cell survival. Therapeutic targeting of the PBX hexapeptide binding pocket using peptide antagonists like HXR9 or clinical candidates like HTL001 disrupts the HOX-PBX complex, leading to the induction of apoptosis in cancer cells while sparing most normal adult tissues. This site represents a significant target for the development of protein-protein interaction inhibitors in oncology.

Other names

PBX1PBX2PBX3PBX4Pre-B-cell leukemia transcription factorTALE homeobox proteinHomeobox protein PBX1Homeobox protein PBX2Homeobox protein PBX3

Competitive inhibition of the protein-protein interaction (PPI) between HOX and PBX proteins by binding to the conserved hydrophobic hexapeptide binding pocket on the PBX homeodomain.