The multiple functions of Numb.

Numb is an evolutionary conserved protein that plays critical roles in cell fate determination. Mammalian Numb displays a higher degree of structural complexity compared to the Drosophila homolog based on the number of encoding genes (Numb and Numb-like) and of alternative spliced isoforms. Accordingly, Numb proteins display a complex pattern of functions such as the control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion, cell migration, ubiquitination of specific substrates and a number of signaling pathways (i.e. Notch, Hedgehog, p53). Recent findings indicate that, besides controlling such physiologic developmental processes, subversion of the above Numb-dependent events plays a critical role in disease (e.g. cancer). We will review here the multiple functions of mNumb and their underlying molecular mechanisms in development and disease. Copyright (c) 2009 Elsevier Inc. All rights reserved.