Pre-B-cell leukemia homeobox protein (PBX)

Pre-B-cell leukemia homeobox (PBX) proteins are a family of TALE-class homeodomain transcription factors, including PBX1, PBX2, PBX3, and PBX4, that act as essential co-factors for Homeobox (HOX) proteins. They facilitate high-affinity DNA binding and regulate gene expression programs crucial for embryogenesis, organogenesis, and hematopoiesis. In cancer, PBX proteins frequently serve as oncogenic drivers; for instance, PBX1 is a key component of the E2A-PBX1 fusion protein in pediatric acute lymphoblastic leukemia, and its overexpression is linked to chemoresistance in ovarian and breast cancers. Therapeutic development has focused on small molecules like T417, which disrupts the PBX-DNA interaction, and cell-permeable peptides like HXR9, which competitively inhibits the interaction between HOX and PBX proteins. These strategies aim to re-sensitize resistant tumors and induce cell death in malignant lineages, although the target's pleiotropic role in normal physiology remains a challenge for clinical translation.

Other names

PBX familyPre-B-cell leukemia transcription factorPre-B-cell leukemia homeoboxHomeobox protein PBXHomeobox protein PRLPBC-class homeodomain protein

Competitive antagonism of the HOX-PBX protein-protein interaction and inhibition of the PBX-DNA binding interface to suppress oncogenic transcription