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

The Filamin A–Core-binding factor subunit beta (FLNA–CBFB) protein–protein interface is a critical regulatory junction that controls the subcellular localization and transcriptional activity of the CBF complex. Filamin A, a large actin-binding scaffold protein, physically interacts with CBFB (also known as PEBP2β) to sequester it within the cytoplasm, thereby preventing its nuclear translocation and subsequent dimerization with RUNX transcription factors (Watanabe et al., 2005; Yoshida et al., 2005). This interaction serves as a checkpoint for various biological processes, including hematopoiesis and chondrogenesis. In the context of disease, the disruption of this interface is a therapeutic strategy; for instance, the small molecule kartogenin binds to Filamin A to release CBFB, promoting its nuclear entry and the activation of RUNX1-mediated gene expression for cartilage repair in osteoarthritis (Johnson et al., 2012). Conversely, in certain leukemias like inv(16) AML, the dysregulation of CBF subunits is a primary driver, and modulating the FLNA–CBFB interaction offers a potential avenue to restore normal transcriptional control (Bushweller, 2019). As a therapeutic target, this interface represents a novel class of protein-protein interactions (PPIs) where small molecules can modulate transcription by altering the mechanical and structural scaffolding of the cell.

Other names

Filamin A–CBFβ interactionFilamin A–PEBP2β interactionFilamin A–CBF-beta complexFLNA-CBFB protein-protein interface

Small molecule disruption of the protein-protein interface to release CBFβ from cytoplasmic sequestration, enabling its nuclear translocation and subsequent activation of RUNX-mediated transcription.