Notch Mutation Effects on NICD Molecules Dimerization

The Notch signaling pathway plays important roles in developmental biology, Immune system, vascular system and variety of other systems. The dysregulation of the notch signaling pathway has led to certain diseases, cancers and developmental malformations. The notch receptors located on the cell surface are activated when it interacts with a ligand that leads to the release of the Notch intracellular domain(NICD) that then translocates to the nucleolus and begins transcription. There are four notch proteins(NICDs) that contain an important Ankyrin domain for NICD homodimerization. The notch 4(NICD) is quite different in structure and how it performs compared to the rest of the group of notches and in unpublished research performed by crow and Albig it was observed that notch4 (N4ICD) displayed a stronger dimerization activity. It is hypothesized that because it is disparate that it is able to dimerize far better than the other notches. Data collected from Crow and Albig found a site where 1-3 NICDs notches coded for a similar amino acid and N4ICD presented a different one. It was speculated that by converting the amino acid to the same one the other NICDs coded that it will convey if there is relation to its dimerization activity strength.