Runt-related transcription factor 1–Core-binding factor subunit beta complex (RUNX1–CBFβ) (RUNX1–CBFβ)

The Runt-related transcription factor 1–Core-binding factor subunit beta (RUNX1–CBFβ) complex, also known as the Core-binding factor (CBF) complex, is a master regulator of hematopoiesis and is essential for the development of all definitive hematopoietic lineages (UniProt P19022, Q13951). The complex consists of the DNA-binding RUNX1 subunit and the non-DNA-binding CBFβ subunit, which stabilizes RUNX1 and significantly increases its affinity for DNA (PMID: 25837516). Genetic alterations involving this complex, such as the t(8;21) and inv(16) chromosomal translocations, are among the most common mutations in acute myeloid leukemia (AML), resulting in the production of oncogenic fusion proteins that disrupt normal gene expression (PMID: 30635431). Because the interaction between RUNX1 and CBFβ is critical for the function of both wild-type and certain oncogenic forms, it has become a high-priority target for drug development. Small molecule inhibitors, such as Ro5-3335 and the AI-10-47 series, have been developed to disrupt this protein-protein interaction (PPI), effectively inhibiting the transcriptional program of leukemic cells and inducing differentiation or apoptosis (PMID: 22343824). Targeting this complex offers a potential therapeutic strategy for leukemias characterized by CBF rearrangements or RUNX1 mutations, though challenges remain regarding the impact on normal hematopoietic stem cell maintenance (PMID: 10648228).

Other names

Core-binding factor complexCBF complexAML1–CBFB complexPEBP2 complexPolyomavirus enhancer-binding protein 2 complex

Inhibition of the protein-protein interaction (PPI) between the RUNX1 Runt domain and the CBFβ subunit to reduce DNA binding and transcriptional activity.