Ligand-Independent Mechanisms of Notch Activity

Interaction between the Notch receptor and Delta-Serrate-Lag2 (DSL) ligands is generally deemed to be the starting point of the Notch signaling cascade, after which, Notch is cleaved and the intracellular domain acts as a transcriptional coactivator. By contrast, Notch protein can become activated independent of ligand stimulus through recently identified endosomal trafficking routes as well as through aberrant regulation of Notch components during Notch trafficking, ubiquitination, and degradation. In this review, we summarize genes implicated in ligand-independent Notch activity and remark on the mechanisms by which this process could occur.