Core binding factor subunit beta (CBFB)

Core binding factor subunit beta (CBFB) is a non-DNA-binding regulatory subunit that forms a heterodimeric complex with Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) to constitute the Core Binding Factor (CBF) [UniProt: Q13951]. This complex serves as a master regulator of definitive hematopoiesis and bone development, where CBFB enhances the DNA-binding affinity of RUNX proteins and stabilizes them against proteolytic degradation [PubMed: 10551804]. CBFB is a significant therapeutic target in Acute Myeloid Leukemia (AML), particularly in cases involving the inv(16)(p13q22) chromosomal rearrangement, which creates the CBFB-MYH11 fusion gene [NIH: Genetics Home Reference]. The resulting CBFB-SMMHC fusion protein acts in a dominant-negative fashion to sequester RUNX1, leading to the repression of RUNX1-mediated transcription and the arrest of myeloid differentiation [PubMed: 25607336]. Experimental small molecules like AI-10-49 have been developed to specifically inhibit the interaction between CBFB-SMMHC and RUNX1, showing promise in restoring normal hematopoietic processes in preclinical models [PubMed: 25607336]. Additionally, CBFB has been identified as a tumor suppressor in breast cancer, where its loss or mutation is associated with increased metastatic potential [PubMed: 25217933].

Other names

CBF-betaPEBP2BPEA2-betaSL3-3 enhancer factor 1 subunit beta

Inhibition of the protein-protein interaction between CBFB (or the CBFB-MYH11 fusion protein) and the RUNX1 Runt domain to restore normal transcriptional regulation and hematopoietic differentiation [PubMed: 25607336].