NUMB (gene)

NUMB is a gene that encodes a protein involved in cell fate determination, particularly during development. It functions as an intrinsic determinant, meaning it influences the developmental pathway a cell will follow based on its own internal composition rather than external signals alone, although it can be modulated by external signals.

The NUMB protein is an endocytic adaptor protein. It interacts with other proteins involved in endocytosis, the process by which cells internalize molecules from their external environment. Specifically, NUMB is involved in the internalization and trafficking of transmembrane receptors, including Notch.

A crucial function of NUMB is its role in asymmetric cell division. During asymmetric cell division, a mother cell divides into two daughter cells with different fates. NUMB segregates into one of the daughter cells, influencing its differentiation pathway. In this context, NUMB often inhibits the Notch signaling pathway in the daughter cell it is inherited by. This inhibition is critical for maintaining the proper balance of cell types during development.

The Notch signaling pathway plays a fundamental role in cell fate decisions, and NUMB acts as a key regulator of this pathway. By controlling the internalization and trafficking of Notch receptors, NUMB modulates Notch signaling activity and, consequently, influences the differentiation of cells during development.

Mutations in the NUMB gene, or altered expression of the NUMB protein, can lead to developmental abnormalities. Dysregulation of NUMB has also been implicated in various cancers, where it can affect cell proliferation and differentiation. Different isoforms of the NUMB protein exist, arising from alternative splicing, and these isoforms may have different functions or regulatory properties.