Mouse Numb Homolog (NUMB) Protein

Background

NUMB endocytic adaptor protein (NUNB) plays a critical role in cell fate determination, particularly in neural progenitor cells, where it antagonizes Notch signaling pathways to promote differentiation and prevent excessive self-renewal. It functions as an adaptor protein in clathrin-mediated endocytosis, facilitating the internalization of membrane receptors and influencing their downstream signaling pathways, including Notch and integrins. The asymmetrical distribution of NUMB during mitosis determines daughter cell fate by regulating receptor-mediated signaling and is crucial for proper neural development. NUMB also interacts with various proteins such as alpha-adaptin, EPS15, and integrins, contributing to cellular processes like adhesion, migration, and polarity. Aberrations in NUMB expression or function have been implicated in cancers, including breast cancer and glioblastoma, where its loss correlates with enhanced Notch signaling and increased tumorigenic potential. In addition to its canonical roles, NUMB has been found to influence p53 stability and activity, further linking it to tumor suppression and apoptosis regulation. Its localization and function are tightly regulated through post-translational modifications, including phosphorylation by kinases like LATS and Aurora A, which affect its stability and interaction partners.