Noncanonical activation of NOTCH3

Stable Identifier
Homo sapiens
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Besides DLL/JAG ligands, NOTCH3 signaling can also be activated by binding of NOTCH3 to YBX1 (YB 1) (Rauen et al. 2009). YBX1, a protein involved in mRNA processing, is secreted by mesangial cells and monocytes during inflammation and acts as an extracellular mitogen (Frye et al. 2009). YBX1 triggers the gamma secretase complex mediated cleavage of NOTCH3, resulting in release of NOTCH3 intracellular domain (NICD3) and activation of NOTCH3 target genes (Rauen et al. 2009).

Literature References
PubMed ID Title Journal Year
19640841 YB-1 acts as a ligand for Notch-3 receptors and modulates receptor activation

Rauen, T, Raffetseder, U, Frye, BC, Djudjaj, S, M├╝hlenberg, PJ, Eitner, F, Lendahl, U, Bernhagen, J, Dooley, S, Mertens, PR

J. Biol. Chem. 2009
19483673 Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen

Frye, BC, Halfter, S, Djudjaj, S, Muehlenberg, P, Weber, S, Raffetseder, U, En-Nia, A, Knott, H, Baron, JM, Dooley, S, Bernhagen, J, Mertens, PR

EMBO Rep. 2009
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