NOTCH1 and neoplasm: NUMB is a tumor suppressor that recruits ubiquitinated E3 ligases to NOTCH receptors, thereby promoting NOTCH1 ubiquitination at the membrane, which induces the degradation of the NOTCH1 intracellular domain (NICD1), thus bypassing its nuclear translocation and downstream activation of NOTCH1 target genes (McGill and McGlade, 2003; McGill et al., 2009).