Cellular retinoic acid-binding protein 2 (CRABP2) (CRABP2)

Cellular retinoic acid-binding protein 2 (CRABP2) is a small intracellular protein that serves as a high-affinity carrier for all-trans-retinoic acid (atRA) (UniProt P29373). It plays a critical role in the retinoic acid signaling pathway by shuttling atRA from the cytoplasm into the nucleus upon ligand binding. Once in the nucleus, CRABP2 physically interacts with the Retinoic Acid Receptor (RAR) through a specific delivery interface, facilitating the direct channeling of atRA into the receptor's ligand-binding pocket (Budhu & Noy, 2002). This mechanism significantly enhances RAR-mediated transcriptional activity, which governs cell differentiation and growth arrest. In clinical contexts, CRABP2 is often viewed as a tumor suppressor in breast cancer, where its presence sensitizes cells to the anti-proliferative effects of retinoids (Schug et al., 2007). Conversely, its absence or a shift in the CRABP2/FABP5 ratio can lead to retinoid resistance or the activation of alternative survival pathways. Understanding the CRABP2-RAR interface is therefore vital for developing strategies to overcome drug resistance in retinoid-based therapies.

Other names

CRABP-IICellular retinoic acid-binding protein IIRBP6Retinoic acid-binding protein II

CRABP2 facilitates the direct transfer of all-trans-retinoic acid (atRA) to the Retinoic Acid Receptor (RAR) by forming a transient protein-protein complex at the delivery interface, a process known as ligand channeling that ensures efficient activation of RAR-mediated transcription (Budhu & Noy, 2002; Dong et al., 1999).