Department of Experimental Medicine, Sapienza University, 324 viale Regina Elena, 00161 Rome, Italy.
Exp Cell Res. 2010 Apr 1;316(6):900-6. doi: 10.1016/j.yexcr.2009.11.017. Epub 2009 Nov 26.
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.
Numb 是一种进化上保守的蛋白质，在细胞命运决定中发挥着关键作用。与果蝇同源物相比，哺乳动物的 Numb 基于编码基因（Numb 和 Numb-like）的数量和选择性剪接异构体的数量显示出更高程度的结构复杂性。因此，Numb 蛋白表现出复杂的功能模式，例如控制不对称细胞分裂和细胞命运选择、内吞作用、细胞黏附、细胞迁移、特定底物的泛素化以及许多信号通路（即 Notch、Hedgehog、p53）。最近的研究结果表明，除了控制这些生理发育过程外，上述依赖于 Numb 的事件的颠覆在疾病（例如癌症）中起着关键作用。在这里，我们将回顾 mNumb 的多种功能及其在发育和疾病中的潜在分子机制。
