MINAR is a novel NOTCH-2 interacting protein that regulates NOTCH-2 activation and angiogenesis
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Angiogenesis, the formation of new vessels, is a highly regulated and complex cellular process, which plays a crucial role in physiological processes such as embryological development and wound healing. Aberrant angiogenesis is a key feature of common human pathologies, including cancer and inflammation. Neurogenic locus notch homology protein 2 (NOTCH2) signaling is an evolutionarily conserved pathway and a major player in regulating angiogenesis. Despite its fundamental involvement in both embryonic development and human diseases, the processes through which the NOTCH pathway modulates angiogenesis are not fully elucidated. We have identified Major Intrinsically disordered NOTCH2-Associated Receptor (MINAR) as a novel ligand for NOTCH2. The main objectives of this project were to demonstrate the mechanism of association between MINAR with NOTCH2, and its biological importance in angiogenesis. Our findings reveal that MINAR is an intrinsically disordered cell surface receptor, which is highly expressed in endothelial cells and other tissues of human vasculature. The physical association between MINAR and NOTCH2 increases its order and stability, and also reduces the degradation of MINAR. Moreover, we demonstrate that MINAR regulates NOTCH2 activation to inhibit angiogenesis. Taken together, the data suggest that MINAR is a novel ligand of NOTCH2 and a key regulator of angiogenesis.