Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).

1. beta1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling PMID: 29269413
2. Expression of translocation-associated notch protein (Notch1) is elevated in patients with chronic hepatitis C (HCV). Inhibition of Notch signaling downregulates HCV-specific Th22 cells and interleukin-22 production, which is accompanied by the reduction of aryl hydrocarbon receptor and modulatory cytokines (IL-6 and tumor necrosis factor-alpha). PMID: 28410452
3. MiR-497 approximately 195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch1 and HIF1A activity. PMID: 28685750
4. The results demonstrated that treatment with norepinephrine(NE) enhanced cell viability and invasion, and inhibited apoptosis of Pancreatic ductal adenocarcinoma (PDAC) cells; however, these effects were suppressed following treatment with Notch1specific siRNA and DAPT. In conclusion, NE may enhance the malignant biological behaviors of PDAC via activating the Notch1 pathway. PMID: 30226612
5. sinonasal inverted papillomas lesions presented reduced Notch-1 expression compared to nasal polyposis. Dysplastic lesions presented low Notch-1 immunopositivity. Enhancement of Notch-1 gene expression was also associated with inflammation. PMID: 30297114
6. NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. PMID: 29743479
7. Notch1 activation and epithelial-mesenchymal transition are coupled to promote squamous cell carcinomas tumor initiation in concert with transforming growth factor (TGF)-beta present in the tumor microenvironment. PMID: 29170450
8. the reported Dowling-Degos mutations of POFUT1, except for M262T, fail to rescue Notch1 signaling efficiently in the CRISPR-engineered POFUT1-/- background; these studies identify POFUT1 as a potential target for cancers driven by Notch1 mutations and provide a structural roadmap for its inhibition PMID: 28334865
9. Study reports that IL-17 stimulation induces NOTCH1 activation in oligodendrocyte progenitor cells, contributing to Th17-mediated demyelinating disease. PMID: 28561022
10. High NOTCH1 expression is associated with endometriosis. PMID: 29398419
11. Mir-34a regulates cigarette smoke extract-induced respiratory endothelial cell apoptosis by targeting Notch-1 protein. PMID: 29373969
12. shear stress was able to induce arterial endothelial differentiation of stem cells from human exfoliated deciduous teeth, and VEGF-DLL4/NotchEphrinB2 signaling was involved in this process. PMID: 30015843
13. Notch1 receptor intracellular domain and Ets-1 cooperatively bind to the DNA of the TRPA1 promoter to up-regulate transcription in the context of living cells. PMID: 28220825
14. miR-139-5p was identified as a tumour suppressor by negatively targeting Notch1, and this work suggests a possible molecular mechanism of the miR-139/Notch1/EMT axis for glioma treatment. PMID: 30170559
15. Data suggest that CBX4 expression is up-regulated in breast cancer and is correlated with unfavorable overall survival; CBX4 promotes cell growth and migration via transcriptionally suppressing expression of miR137 to trigger Notch1 signaling pathway. (CBX4 = chromobox homolog 4; miR137 = microRNA 137; Notch1 = neurogenic locus notch homolog protein-1) PMID: 29229426
16. Data indicate that stanniocalcin 1 (STC1) is a non-canonical NOTCH1 ligand and acts as a crucial regulator of stemness in glioblastoma (GBM). PMID: 29196129
17. showed here that 3' UTR NOTCH1 mutations are associated with low CD20 expression and with relative resistance to anti-CD20 immunotherapy in vitro PMID: 28550186
18. MiR92a3p blocks the progression of Wilms tumor by targeting NOTCH1. PMID: 29845267
19. identified a branch of the XIST/miR-137/Notch-1 pathway that regulates proliferation and TGF-beta1-induced EMT in NSCLC, which could be involved in NSCLC progression PMID: 29812958
20. In conclusion, we demonstrated that EV71 infection induced elevated expressions of TLR3/4 and Notch1/2 in CD14+ monocytes. PMID: 29702280
21. Data show that fluid shear stress activates NOTCH signaling, which upregulates GJA4 (commonly, Cx37) and downstream cell cycle inhibitor CDKN1B (p27). PMID: 29247167
22. EZH2 mutations coexisted with mutations of NOTCH1, IL7R, and PHF6 in the two Adult T-cell Acute Lymphoblastic Leukemia patients, and they responded poorly to chemotherapy and experienced difficult clinical histories and inferior outcomes PMID: 28747286
23. Crosstalk between TLR4 and Notch1 signaling regulates the inflammatory response in the IgAN and maybe plays an important role in the progression of IgAN. PMID: 29230705
24. These results suggest that gastric cancer progression is not associated with a unique signaling pathway and that a feedback loop may exist between the HGF/c-Met and Notch1 signaling pathways, which may result in therapeutic resistance. PMID: 29781036
25. Results indicated that CRNDE functioned as an oncogene in osteosarcoma cell lines, and CRNDE may exert its oncogenic role via regulating Notch1 signaling and EMT in osteosarcoma. PMID: 29246789
26. NOTCH1 is a central mediator of TGFbetamediated FOXP3 expression and NOTCH1 inhibition produces a significant reduction of melanoma cell proliferation and viability. PMID: 29620159
27. Study observed membranous Notch1 expression in 31% of the oral leukoplakia (OL) samples. Membranous Notch1 expression was significantly associated with the severity of dysplasia and development of oral squamous cell carcinoma (OSCC). Also, the extent of membranous Notch1 expression was found to increase during carcinogenesis. PMID: 29620248
28. High NOTCH1 expression is associated with head and neck squamous cell carcinoma. PMID: 29047105
29. Notch1 role in the angiomyolipoma differentiation.Rheb transcription is regulated by direct Notch1 binding to the Rheb promoter. PMID: 29184052
30. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance. PMID: 29686529
31. we demonstrate for the first time the presence of NOTCH1 mutation in cases of Hodgkin transformation of B-CLL and outline the clinicopathological characteristics and treatment outcomes for these patients. PMID: 27686521
32. Endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. PMID: 29158473
33. Notch1 activation in glioma stem cells specifically induces expression of the long noncoding RNA, TUG1. PMID: 27922002
34. B-AP15 induced cytotoxic response to hepatocellular carcinoma cells by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. PMID: 29454609
35. Notch1 is a direct target of miR-449a and positively regulated by circRNA-000911 in breast cancer cell lines. PMID: 29431182
36. human thymopoiesis involves complex spatiotemporal regulation of Notch ligand expression, which ensures the coordinated delivery of niche-specific NOTCH1 signals required for dynamic T-cell development. PMID: 30042180
37. Notch1 was confirmed as a target of miR1395p and, showed a marked downregulated expression together with its pathway downstream factors during mesenchymal stem cells osteogenesis. PMID: 29565453
38. High expression of NOTCH1 was associated with better overall survival in head and neck squamous cell carcinoma. PMID: 29533972
39. This study identifies the unique role of JAG1-induced Notch activation in the pathogenesis of multiple myeloma PMID: 29242532
40. Results indicate that lncRNA SNHG1 may be a potential predictor of prognosis in esophageal squamous cell cancer (ESCC) patients, and that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 expression levels in ESCC cells. PMID: 29081407
41. ATRX, NOTCH1 and NOTCH2 expression varies in angiosarcomas and shows significant correlations with site of origin and poor clinical outcome PMID: 28796347
42. CK2 inhibitor CX-4945 destabilizes NOTCH1 and synergizes with JQ1 against human T-acute lymphoblastic leukemic cells. PMID: 27758824
43. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we found a link among HBx, the Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced hepatocellular carcinoma (HCC) cell survival and could be a therapeutic target for HCC treatment. PMID: 29048612
44. Notch 1 was key in the progression of breast cancer, and knocking down the expression of Notch 1 significantly suppressed the proliferation and invasion of breast cancer cells. PMID: 29207146
45. Results provide insight into the interrelationship between T-ALL oncogenic networks and the therapeutic efficacy of dual PI3Kgamma/delta inhibition in the context of NOTCH1 and cMYC signaling. PMID: 28716817
46. Notch1 signaling is an essential downstream pathway of MDM2 in mediating high glucose-induced mitotic catastrophe in podocytes. PMID: 28643424
47. Effect of Notch1 gene on proliferation and chemo sensitivity of lung cancer A549 cells was studied. PMID: 28678318
48. results indicate that an ATP2C1/NOTCH1 axis might be critical for keratinocyte function and cutaneous homeostasis, suggesting a plausible model for the pathological features of Hailey-Hailey disease PMID: 27528123
49. MAFB enhanced leukemogenesis by the naturally occurring Notch1 mutants, decreased disease latency, and increased disease penetrance. PMID: 29138297
50. the tumorsuppressive roles of miR455 in modulating EOC proliferation and invasion through regulation of Notch1 expression. PMID: 29039517

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Cell membrane; Single-pass type I membrane protein.; [Notch 1 intracellular domain]: Nucleus.

NOTCH family

In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.

HGNC: 7881

OMIM: 109730

KEGG: hsa:4851

STRING: 9606.ENSP00000277541

UniGene: Hs.495473