Filamin A – Core-binding factor subunit beta protein–protein interaction interface (FLNA–CBFB PPI)

The Filamin A – Core-binding factor subunit beta (CBFβ) protein–protein interaction interface is a critical regulatory site where the actin-binding scaffold protein Filamin A (FLNA) binds to and stabilizes the CBFβ subunit (UniProt P21333, PMID: 25605871). CBFβ is an essential co-factor for the RUNX family of transcription factors, which govern key aspects of hematopoiesis and myeloid differentiation (UniProt Q13951, PMID: 21135250). In certain malignancies, particularly Acute Myeloid Leukemia (AML) with the inv(16) chromosomal rearrangement, the resulting CBFB-MYH11 fusion protein hijacks this interaction to maintain its stability and promote leukemogenesis (PMID: 25605871, PMID: 14724304). Research indicates that Filamin A protects CBFβ from proteasomal degradation, making this interface a potential therapeutic target for leukemic cells that depend on high levels of CBFβ or its fusion variants (PMID: 25605871). Therapeutic strategies aiming to disrupt this interface seek to induce the degradation of CBFβ, thereby inhibiting the RUNX1-mediated transcriptional programs necessary for cancer cell survival (PMID: 21135250, PMID: 14724304). While no drugs targeting this specific interface are currently approved for clinical use, experimental small molecules and peptidomimetics are being explored in preclinical models (PMID: 25605871). A significant challenge in targeting this interface is the ubiquitous nature of Filamin A and its involvement in diverse cellular processes, which necessitates high specificity to avoid systemic toxicity (UniProt P21333, PMID: 21135250).

Other names

FLNA–CBFB interactionFilamin A – CBF-beta PPIFilamin A – Core-binding factor subunit beta interface

Disruption of the protein-protein interaction to induce degradation of CBFβ and/or CBFB-MYH11 fusion proteins, thereby inhibiting RUNX1-mediated leukemogenic gene expression (PMID: 25605871, PMID: 21135250).