NOTCH-1

Official Full Name

notch receptor 1

Organism

Homo sapiens

GeneID

4851

Background

This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]

Synonyms

NOTCH1; hN1; AOS5; TAN1; AOVD1;

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Detailed Information

Notch-1 is a member of the Notch gene family. The Notch-1 signaling pathway plays an important role in cell proliferation, differentiation, survival, and apoptosis. Its abnormal expression is closely related to the occurrence and development of tumors. In vitro and animal experiments have confirmed that activated Notch-1 can transform normal cells into malignant cells and has abnormal expression in many solid tumors and hematological tumors in humans. Notch-1 is a type I transmembrane protein family that has dual functions of cell surface receptors and nuclear transcriptional regulation. Notch-1 signal transduction occurs mainly between cells, and its ligand is also a transmembrane molecule. The Notch-1 receptor forms a heterodimer through a disulfide bond between the cysteine-rich LIN repeat and the transmembrane region. This dimer is paired with a basic amino acid protease-like protein in the Golgi apparatus. Furine cleaves into the active Notch-1 protein receptor, which can be activated by Jagged-1 ligand.

Notch-1 Figure 1. NOTCH1 protein structure and signaling activation. (Emanuela, R. , et al. 2018)

Notch-1 Signaling Pathway

Abnormal Notch-1 signals are closely related to the occurrence of some tumors. Disturbances in Notch-1 signals can not only directly cause tumors, but also can ultimately induce tumors directly or indirectly through interaction with other signaling pathways. Current research indicates that the Notch-1 signal may be an important meeting point for multiple pathways. Intracellular Notch-1 dysfunction can prevent cell differentiation and eventually induce undifferentiated cells to transform into malignant cells. In some tumors, it can induce cell cycle arrest, inhibit growth and induce apoptosis, and also induce epithelial-mesenchymal transition to maintain tumor cell phenotype.

The study found that the positive expression rate of Notch-1 in ovarian cancer was significantly higher than that of ovarian cystadenomas and normal ovarian epithelial tissues, and it increased with the increase of pathological grade. Notch-1 Receptor As a member of the Notch receptor family that is often concerned, it plays an important role in regulating the growth, proliferation and apoptosis of tumor cells. Notch-1 receptor and its ligand Jagged-1 expression are often used in the diagnosis and prognosis of cancer. Studies have found that patients with negative Notch-1 expression in tumor tissue are prone to relapse and metastasis. A negative Notch-1 expression may be one of the risk factors for early recurrence and metastasis of esophageal squamous cell carcinoma. Patients with this risk factor suggest that early postoperative adjuvant chemotherapy is needed. The expression level of Jagged-1 can be used as an independent prognostic factor for judging the prognosis of renal clear cell carcinoma, and high expression of Jagged-1 indicates a poor prognosis of renal cancer.

Notch-1 and Tumor Treatment

Notch-1 serves as a molecular target for treating tumors. Studies have shown that 50% of patients with T-cell acute lymphoblastic leukemia have an active Notch-1 gene mutation, suggesting that it may be an ideal target for molecular therapy. Bioinformatics software predicts that miR-34a and 3'UTR of Notch-1 are highly homologous. Overexpression of miR-34a can reduce the expression of target gene Notch-1 and inhibit the proliferation of bladder tumor cells. It was found that SiRNA targeting the Notch-1 gene can inhibit tumor growth and promote apoptosis in nude mice. The mechanism may be closely related to changes in bal-2 and bax expression. Nanotechnology was used to construct the vector and increase the expression of miR-144 to down-regulate the target gene Notch-1, thereby inhibiting the growth of colon cancer cells. Studies have shown that Notch-1 inhibits colon cancer cell growth by interacting with the Akt / NF-κB / mTOR signaling pathway.

References:

Emanuela, R. , Stefano, B. , Filomena, D. F. , Beatrice, D. P. , Erica, D. , & Chiara, R. , et al. (2018). Notch1 aberrations in chronic lymphocytic leukemia. Frontiers in Oncology, 8, 229-.
Nowell, C. S. , & Radtke, F. . (2017). Notch as a tumour suppressor. Nature Reviews Cancer, 17(3), 145-159.
Andrieu, G. , Tran, A. H. , Strissel, K. J. , & Denis, G. V. . (2016). Brd4 regulates breast cancer dissemination through jagged1/notch1 signaling. Cancer Research, 0008-5472.CAN-16-0559.

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