Figure 1.

NOTCH signaling is essential for HNSCC suppression. (a) Schematic representing the long-tail genes mutated in HNSCC patients (adapted from Loganathan et al.) (b) Ligands Jagged1/2 (JAG1/2) binding results in ADAM10 (Disintegrin and metalloproteinase domain-containing protein 10) and gamma secretase-mediated cleavage of NOTCH1/2 leading to release of NOTCH intracellular domain (NICD). AJUBA sequesters NUMB, thereby blocking ubiquitination and degradation of NICD. NICD translocates to the nucleus, binds to transcription factor RBPJ, and turns on the expression of Notch target genes that include HNSCC tumor suppressors identified in our in vivo CRISPR screen.