The neurogenic locus notch homolog protein 3 is a protein encoded by the NOTCH3 gene. There are 4 notch receptors in mammals, all of which are transmembrane proteins and notch signalling regulates a very diverse set of biological functions; The most commun is the cell lineage determination. Therefore, changes in the activity of these receptors is associated with various benign and malignant diseases as T-ALL (T-lineage acute lymphoblastic leukemia). T-ALL is characterized by the uncontrolled proliferation of T-cell lymphoblasts in the blood, the brown marrow and the tissues.
Function
NOTCH family : The NOTCH family encodes transmembrane receptor proteins that are involved in cell fate determination during development. In the drosophila [1] adult midgut, intestinal stem
cells produce two types of daughter cells, the nutrient-absorbing enterocytes (ECs) and secretory enteroendocrine (ee) cells. Notch signalling between intestinal stem cells and their daughter cells guides cell specification. ISCs with elevated levels of the Notch Delta ligand more primarily activate the Notch signalling pathway in daughter cells and cause them to become ECs. However, ISCs having low levels of Notch Delta ligand direct daughter cells to become ee cells.
The NOTCH gene family in humans [2] has a link with the Drosophila Notch gene. Members of the NOTCH gene family encode transmembrane receptor proteins that are useful to determine the cell fate during development.
5CZX : 5CZX receives a signal and transmits it in the cell to initiate a change in cell activity.It can also used in the neuron fate commitment, artery morphogenesis or the regulation of NOTCH signaling pathway
Disease
It is understood that the Notch receptors play an important role in cancer development in mammals. These oncogenic mechanisms of the Notch receptors are dependant on its intracelluclar signaling. Therefore, in order to understand how the cancer develops due to these receptors, it is necessary to understand the Notch pathway
The target genes in the Notch pathway are expressed by a variety of translocation, post-translational modifications and activation of ligands associated to it. Following translation, Furin-like convertase modifies the Notch receptor by proteolytic cleavage at site 1 (S1).
Relevance
The Notch signaling pathway regulates cell-cell interaction, embryogenesis as well as various other biological functions in adult tissues. It is a highly conserved pathway. Its relevance and clinical significance lie in the mutations in the Notch gene that have been identified in an extensive range of cancers in mammals. These mutations can change the activity of the pathway rendering it capable of causing various diseases depending on the sub-type of the Notch receptor and more importantly, causing it to play an oncogenic or tumor-suppressive role. [3]
The Notch signaling pathway has been studied comprehensively and various aspects of this pathway are very well known. Despite this, it is essential to study the pathway further, so as to understand the role it plays in cancer development and explore novel treatment strategies focusing on the Notch pathway.
Structural highlights
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