Filamin A – Core-binding factor subunit beta interface (FLNA–CBFβ interface)

Filamin A (FLNA) is a high-molecular-weight actin-binding protein that serves as a scaffold for over 90 different partners, facilitating cell signaling and cytoskeletal remodeling (UniProt P21333). Core-binding factor subunit beta (CBFβ) is a crucial co-factor for the RUNX family of transcription factors, which are essential for normal hematopoiesis (UniProt Q13951). The Filamin A – CBFβ interface is a significant protein-protein interaction (PPI) that regulates the cytoplasmic-nuclear trafficking of CBFβ and its associated proteins. In Acute Myeloid Leukemia (AML) characterized by the inv(16) mutation, the CBFβ-SMMHC fusion protein interacts with Filamin A, leading to the sequestration of the RUNX1/CBFβ complex in the cytoplasm and the subsequent block of myeloid differentiation (PubMed 25665011). Therapeutic targeting of this interface aims to disrupt the oncogenic scaffolding function of Filamin A, thereby restoring the transcriptional activity of RUNX1 and promoting leukemia cell differentiation. Experimental small molecules like AI-10-49 have been developed to target the CBFβ-SMMHC complex, demonstrating the potential of disrupting these interactions to treat inv(16) AML (PubMed 25678665).

Other names

FLNA-CBFB interactionFilamin-A/CBF-beta complexCBF-beta/Filamin-A interface

Inhibition of the protein-protein interaction between Filamin A and CBFβ (or the CBFβ-SMMHC fusion) to prevent cytoplasmic sequestration of the RUNX1/CBFβ complex and restore nuclear transcriptional activity.