NOTCH2

Summary

Gene Symbol: NOTCH2
Description: notch 2
Alias: AGS2, HJCYS, hN2, neurogenic locus notch homolog protein 2, Notch homolog 2
Species: human
Products:     NOTCH2

Top Publications

  1. Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, et al. Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2. Mol Cell Biol. 2000;20:6913-22 pubmed
    ..In this report, we investigated these issues for Notch2. All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells, although characteristics ..
  2. Lin X, Song K, Lim N, Yuan X, Johnson T, Abderrahmani A, et al. Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study. Diabetologia. 2009;52:600-8 pubmed publisher
    ..In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited. ..
  3. Blaumueller C, Qi H, Zagouras P, Artavanis Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997;90:281-91 pubmed
    ..We provide evidence that these fragments are tethered together on the plasma membrane by a link that is sensitive to reducing conditions, forming a heterodimeric receptor. ..
  4. Grarup N, Andersen G, Krarup N, Albrechtsen A, Schmitz O, Jørgensen T, et al. Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged D. Diabetes. 2008;57:2534-40 pubmed publisher
    ..the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), ADAMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of genome-wide association data...
  5. Stancakova A, Kuulasmaa T, Paananen J, Jackson A, Bonnycastle L, Collins F, et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009;58:2129-36 pubmed publisher
    ..TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed...
  6. Wang N, Sanborn Z, Arnett K, Bayston L, Liao W, Proby C, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011;108:17761-6 pubmed publisher
    ..We identified NOTCH1 or NOTCH2 mutations in ~75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most ..
  7. Krikelis D, Pentheroudakis G, Goussia A, Siozopoulou V, Bobos M, Petrakis D, et al. Profiling immunohistochemical expression of NOTCH1-3, JAGGED1, cMET, and phospho-MAPK in 100 carcinomas of unknown primary. Clin Exp Metastasis. 2012;29:603-14 pubmed publisher
    ..001). Our study points to the MAPK and cMET axes as crucial in defining cancer progression and outcome in CUP patients and, if validated, could justify attempts at their therapeutic modulation. ..
  8. Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220-32 pubmed publisher
    ..Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes ..
  9. Kiel M, Velusamy T, Betz B, Zhao L, Weigelin H, Chiang M, et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012;209:1553-65 pubmed publisher
    ..In particular, we identified recurrent somatic gain-of-function mutations in NOTCH2, a gene encoding a protein required for marginal zone B cell development, in 25 of 99 (?25%) cases of SMZL and in ..
  10. Herr F, Schreiner I, Baal N, Pfarrer C, Zygmunt M. Expression patterns of Notch receptors and their ligands Jagged and Delta in human placenta. Placenta. 2011;32:554-63 pubmed publisher
    ..The receptors Notch2, -3, -4 and their ligands Jagged1, -2 and Delta1, -4 were detected at both the mRNA and protein level in early and ..

Detail Information

Publications83

  1. Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, et al. Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2. Mol Cell Biol. 2000;20:6913-22 pubmed
    ..In this report, we investigated these issues for Notch2. All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells, although characteristics ..
  2. Lin X, Song K, Lim N, Yuan X, Johnson T, Abderrahmani A, et al. Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study. Diabetologia. 2009;52:600-8 pubmed publisher
    ..In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited. ..
  3. Blaumueller C, Qi H, Zagouras P, Artavanis Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997;90:281-91 pubmed
    ..We provide evidence that these fragments are tethered together on the plasma membrane by a link that is sensitive to reducing conditions, forming a heterodimeric receptor. ..
  4. Grarup N, Andersen G, Krarup N, Albrechtsen A, Schmitz O, Jørgensen T, et al. Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged D. Diabetes. 2008;57:2534-40 pubmed publisher
    ..the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), ADAMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of genome-wide association data...
  5. Stancakova A, Kuulasmaa T, Paananen J, Jackson A, Bonnycastle L, Collins F, et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009;58:2129-36 pubmed publisher
    ..TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed...
  6. Wang N, Sanborn Z, Arnett K, Bayston L, Liao W, Proby C, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011;108:17761-6 pubmed publisher
    ..We identified NOTCH1 or NOTCH2 mutations in ~75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most ..
  7. Krikelis D, Pentheroudakis G, Goussia A, Siozopoulou V, Bobos M, Petrakis D, et al. Profiling immunohistochemical expression of NOTCH1-3, JAGGED1, cMET, and phospho-MAPK in 100 carcinomas of unknown primary. Clin Exp Metastasis. 2012;29:603-14 pubmed publisher
    ..001). Our study points to the MAPK and cMET axes as crucial in defining cancer progression and outcome in CUP patients and, if validated, could justify attempts at their therapeutic modulation. ..
  8. Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220-32 pubmed publisher
    ..Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes ..
  9. Kiel M, Velusamy T, Betz B, Zhao L, Weigelin H, Chiang M, et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012;209:1553-65 pubmed publisher
    ..In particular, we identified recurrent somatic gain-of-function mutations in NOTCH2, a gene encoding a protein required for marginal zone B cell development, in 25 of 99 (?25%) cases of SMZL and in ..
  10. Herr F, Schreiner I, Baal N, Pfarrer C, Zygmunt M. Expression patterns of Notch receptors and their ligands Jagged and Delta in human placenta. Placenta. 2011;32:554-63 pubmed publisher
    ..The receptors Notch2, -3, -4 and their ligands Jagged1, -2 and Delta1, -4 were detected at both the mRNA and protein level in early and ..
  11. O Neill C, Urs S, Cinelli C, Lincoln A, Nadeau R, Leon R, et al. Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol. 2007;171:1023-36 pubmed
    Notch functions as an oncogene or tumor inhibitor in various cancers, and decreases in Notch2 expression are associated with increasing grade of human breast cancer...
  12. Otti G, Saleh L, Velicky P, Fiala C, Pollheimer J, Knöfler M. Notch2 controls prolactin and insulin-like growth factor binding protein-1 expression in decidualizing human stromal cells of early pregnancy. PLoS ONE. 2014;9:e112723 pubmed publisher
    ..Immunofluorescence of first trimester decidual tissues revealed expression of Notch2 receptor and its putative, membrane-anchored interaction partners Jagged1, Delta-like (DLL) 1 and DLL4 in stromal ..
  13. Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638-45 pubmed publisher
    ..2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions...
  14. Lee S, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, et al. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009;100:920-6 pubmed
    ..b>Notch2, another member of the Notch gene family, is preferentially expressed in mature B cells and is essential for ..
  15. Simpson M, Irving M, Asilmaz E, Gray M, Dafou D, Elmslie F, et al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet. 2011;43:303-5 pubmed publisher
    We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss...
  16. Wang H, Tian Y, Wang J, Phillips K, Binch A, Dunn S, et al. Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells: implications in intervertebral disc degeneration. J Biol Chem. 2013;288:16761-74 pubmed publisher
    ..Moreover, treatment increased activity of a 2-kb NOTCH2 promoter...
  17. Florena A, Tripodo C, Guarnotta C, Ingrao S, Porcasi R, Martorana A, et al. Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients. Pathobiology. 2007;74:317-22 pubmed
  18. Boulay J, Miserez A, Zweifel C, Sivasankaran B, Kana V, Ghaffari A, et al. Loss of NOTCH2 positively predicts survival in subgroups of human glial brain tumors. PLoS ONE. 2007;2:e576 pubmed
    ..We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0...
  19. Lango H, Palmer C, Morris A, Zeggini E, Hattersley A, McCarthy M, et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes. 2008;57:3129-35 pubmed publisher
    ..Further studies are needed to assess whether individuals with extreme numbers of risk alleles may benefit from genetic testing. ..
  20. Staiger H, Machicao F, Kantartzis K, Schäfer S, Kirchhoff K, Guthoff M, et al. Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes. PLoS ONE. 2008;3:e3019 pubmed publisher
    ..SNPs) JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8/LGR5 rs7961581, THADA rs7578597, ADAMTS9 rs4607103, NOTCH2 rs10923931, DCD rs1153188, VEGFA rs9472138, and BCL11A rs10490072...
  21. Artavanis Tsakonas S, Rand M, Lake R. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770-6 pubmed
    ..Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis. ..
  22. Wu L, Aster J, Blacklow S, Lake R, Artavanis Tsakonas S, Griffin J. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000;26:484-9 pubmed
    ..These studies provide a molecular mechanism to explain the genetic links between mastermind and Notch in Drosophila and indicate that MAML1 functions as a transcriptional co-activator for NOTCH signalling. ..
  23. Sakata Yanagimoto M, Chiba S. Notch2 and immune function. Curr Top Microbiol Immunol. 2012;360:151-61 pubmed publisher
    b>Notch2 is expressed in many cell types of most lineages in the hematolymphoid compartment and has specific roles in differentiation and function of various immune cells...
  24. Sanghera D, Been L, Ortega L, Wander G, Mehra N, Aston C, et al. Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. J Hum Genet. 2009;54:162-8 pubmed publisher
    A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians...
  25. Isidor B, Lindenbaum P, Pichon O, Bezieau S, Dina C, Jacquemont S, et al. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat Genet. 2011;43:306-8 pubmed publisher
    ..of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them...
  26. Thomas G, Jacobs K, Kraft P, Yeager M, Wacholder S, Cox D, et al. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet. 2009;41:579-84 pubmed publisher
    ..10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24...
  27. Ungerbäck J, Elander N, Grünberg J, Sigvardsson M, Söderkvist P. The Notch-2 gene is regulated by Wnt signaling in cultured colorectal cancer cells. PLoS ONE. 2011;6:e17957 pubmed publisher
    ..Furthermore our data supports the notion that additional genes in the Notch pathway might be transcriptionally regulated by Wnt signaling in colorectal cancer. ..
  28. Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, et al. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012;209:1537-51 pubmed publisher
    ..Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting ..
  29. Xu P, Zhang A, Jiang R, Qiu M, Kang C, Jia Z, et al. The different role of Notch1 and Notch2 in astrocytic gliomas. PLoS ONE. 2013;8:e53654 pubmed publisher
    ..However, in our previous study, we found that Notch1 was overexpressed while Notch2 downregulated in the majority of astrocytic gliomas with different grades as well as in glioblastoma cell lines ..
  30. Sriuranpong V, Borges M, Ravi R, Arnold D, Nelkin B, Baylin S, et al. Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res. 2001;61:3200-5 pubmed
    ..Recombinant adenoviruses were used to overexpress active forms of Notch1, Notch2, or the Notch effector protein human hairy enhancer of split-1 (HES1) in DMS53 and NCI-H209 SCLC cells...
  31. Jundt F, Pröbsting K, Anagnostopoulos I, Muehlinghaus G, Chatterjee M, Mathas S, et al. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood. 2004;103:3511-5 pubmed
    ..Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo. ..
  32. Gordon W, Vardar Ulu D, Histen G, Sanchez Irizarry C, Aster J, Blacklow S. Structural basis for autoinhibition of Notch. Nat Struct Mol Biol. 2007;14:295-300 pubmed
    ..We present here the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited conformation...
  33. Lee S, Jeong E, Yoo N, Lee S. Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias. APMIS. 2007;115:1357-63 pubmed publisher
    NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies...
  34. Sivasankaran B, Degen M, Ghaffari A, Hegi M, Hamou M, Ionescu M, et al. Tenascin-C is a novel RBPJkappa-induced target gene for Notch signaling in gliomas. Cancer Res. 2009;69:458-65 pubmed publisher
    ..In these malignant gliomas as well as in GBM cell lines, we found Notch2 protein to be strongly expressed...
  35. Espinosa L, Inglés Esteve J, Aguilera C, Bigas A. Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. J Biol Chem. 2003;278:32227-35 pubmed
    ..In this study, we show that GSK-3 beta is able to bind and phosphorylate Notch2 in vitro and in vivo...
  36. Hu Q, Ang B, Karsak M, Hu W, Cui X, Duka T, et al. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell. 2003;115:163-75 pubmed
    ..This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense ..
  37. Parr C, Watkins G, Jiang W. The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer. Int J Mol Med. 2004;14:779-86 pubmed
    ..These results support the notion that suppression of Notch-1 activity may represent a novel therapeutic strategy. ..
  38. Trøen G, Wlodarska I, Warsame A, Hernández Llodrà S, De Wolf Peeters C, Delabie J. NOTCH2 mutations in marginal zone lymphoma. Haematologica. 2008;93:1107-9 pubmed publisher
  39. Meigs J, Shrader P, Sullivan L, McAteer J, Fox C, Dupuis J, et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med. 2008;359:2208-19 pubmed publisher
    ..A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. ..
  40. Del Bianco C, Vedenko A, Choi S, Berger M, Shokri L, Bulyk M, et al. Notch and MAML-1 complexation do not detectably alter the DNA binding specificity of the transcription factor CSL. PLoS ONE. 2010;5:e15034 pubmed publisher
  41. Cai B, Zheng Y, Ma S, Xing Q, Wang X, Yang B, et al. BANCR contributes to the growth and invasion of melanoma by functioning as a competing endogenous RNA to upregulate Notch2 expression by sponging miR?204. Int J Oncol. 2017;51:1941-1951 pubmed publisher
    ..We identified that miR?204 was a direct target of BANCR and neurogenic locus notch homolog protein 2 (Notch2) was a direct target of miR?204...
  42. Rawal R, Joshi M, Bhargava P, Shaikh I, Pandit A, Patel R, et al. Tobacco habituated and non-habituated subjects exhibit different mutational spectrums in head and neck squamous cell carcinoma. 3 Biotech. 2015;5:685-696 pubmed publisher
    ..In addition to this NOTCH1, NOTCH2, and NOTCH4 gene were found to be mutated only in habitual subjects...
  43. Tchorz J, Tome M, Cloëtta D, Sivasankaran B, Grzmil M, Huber R, et al. Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry. Cell Death Dis. 2012;3:e325 pubmed publisher
    ..b>Notch2 is highly expressed in glioblastoma multiforme (GBM), a highly malignant astrocytoma...
  44. Wang Z, Li Y, Kong D, Banerjee S, Ahmad A, Azmi A, et al. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69:2400-7 pubmed publisher
  45. Wang Z, Plasschaert L, Aryal S, Renaud N, Yang Z, Choo Wing R, et al. TRRAP is a central regulator of human multiciliated cell formation. J Cell Biol. 2018;: pubmed publisher
    ..signaling pathway modulation, and genomic approaches, we show that (a) TRRAP acts downstream of the Notch2-mediated basal progenitor cell fate decision and upstream of Multicilin to control MCC differentiation; and (b) ..
  46. Schauerte C, Hübner A, Rong S, Wang S, Shushakova N, Mengel M, et al. Antagonism of profibrotic microRNA-21 improves outcome of murine chronic renal allograft dysfunction. Kidney Int. 2017;92:646-656 pubmed publisher
    ..b>Notch2 receptor was identified as a potential target of miR-21a-5p and validated by luciferase gene reporter assays...
  47. Colombo M, Galletti S, Bulfamante G, Falleni M, Tosi D, Todoerti K, et al. Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche. Oncotarget. 2016;7:56013-56029 pubmed publisher
    ..This study indicates that high gene expression levels of Notch signaling members (JAG1, NOTCH2, HES5 and HES6) correlate with malignant progression or high-risk disease, and Notch signaling may participate in ..
  48. McDaniell R, Warthen D, Sanchez Lara P, Pai A, Krantz I, Piccoli D, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006;79:169-73 pubmed
    ..JAG1 mutations, we screened 11 JAG1 mutation-negative probands with AGS for alterations in the gene for the Notch2 receptor (NOTCH2). We found NOTCH2 mutations segregating in two families and identified five affected individuals...
  49. Quillard T, Devalliere J, Coupel S, Charreau B. Inflammation dysregulates Notch signaling in endothelial cells: implication of Notch2 and Notch4 to endothelial dysfunction. Biochem Pharmacol. 2010;80:2032-41 pubmed publisher
    ..ECs, TNF? strongly modulates the pattern of Notch expression by decreasing Notch4 expression while increasing Notch2 expression...
  50. Gidfar S, Afsharkhamseh N, Sanjari S, Djalilian A. Notch Signaling in Meibomian Gland Epithelial Cell Differentiation. Invest Ophthalmol Vis Sci. 2016;57:859-65 pubmed publisher
    ..Human meibomian gland epithelial cell expressed Notch1, Notch2, Notch3, Jagged1, Jagged2, Delta-like 1, and Delta-like 3...
  51. Mu X, Liao X, Chen X, Li Y, Wang M, Shen C, et al. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms. J Hazard Mater. 2015;298:232-40 pubmed publisher
    ..DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components...
  52. Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H. Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation. J Biol Chem. 2001;276:25753-8 pubmed
    ..Although both manic fringe (mFng) and lunatic fringe (lFng) decreased the binding of Jagged1 to Notch2 and not that of Delta1, the decrease by mFng was greater in degree than that by lFng...
  53. Liu X, Sheng H, Ma R, Yang J, Luo W, Yang X, et al. Notch signaling is active in normal mouse middle ear epithelial cells. Exp Ther Med. 2016;11:1661-1667 pubmed
    ..study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immuno?uorescence...
  54. Mitsiadis T, Romeas A, Lendahl U, Sharpe P, Farges J. Notch2 protein distribution in human teeth under normal and pathological conditions. Exp Cell Res. 2003;282:101-9 pubmed
    ..have shown that although the Notch1, -2, and -3 receptors are expressed in developing and injured rodent teeth, Notch2 expression was predominant after a lesion...
  55. Hu S, Fu W, Li T, Yuan Q, Wang F, Lv G, et al. Antagonism of EGFR and Notch limits resistance to EGFR inhibitors and radiation by decreasing tumor-initiating cell frequency. Sci Transl Med. 2017;9: pubmed publisher
    ..Our data show that dual targeting of EGFR and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong ..
  56. Johansson P, Klein Hitpass L, Grabellus F, Arnold G, Klapper W, Pförtner R, et al. Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas. Oncotarget. 2016;7:62627-62639 pubmed publisher
    ..Mutations in NOTCH1 and NOTCH2 were each found in 8% of cases, indicating a pathogenetic function of these factors in OAML...
  57. Hammad H, Vanderkerken M, Pouliot P, Deswarte K, Toussaint W, Vergote K, et al. Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10. Nat Immunol. 2017;18:313-320 pubmed publisher
    b>Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related...
  58. Wang C, Zhang W, Zhang L, Chen X, Liu F, Zhang J, et al. miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2. Br J Cancer. 2016;115:1548-1554 pubmed publisher
    ..Invasion assay, qRT-PCR and western blotting were used to validate the roles of miR-146a-5p and Notch2 in EMT progression...
  59. Sakka S, Gafni R, Davies J, Clarke B, Tebben P, Samuels M, et al. Bone Structural Characteristics and Response to Bisphosphonate Treatment in Children With Hajdu-Cheney Syndrome. J Clin Endocrinol Metab. 2017;102:4163-4172 pubmed publisher
    Hajdu-Cheney syndrome (HJCYS) is a rare, multisystem bone disease caused by heterozygous mutations in the NOTCH2 gene...
  60. Zeuner A, Francescangeli F, Signore M, Venneri M, Pedini F, Felli N, et al. The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis. Cell Death Differ. 2011;18:371-80 pubmed publisher
    ..of primary human differentiating erythroblasts, we found that SCF induces an increase in the expression of Notch2, a member of the Notch family implicated in the control of cell growth and differentiation...
  61. Zhao W, Petit E, Gafni R, Collins M, Robey P, Seton M, et al. Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome. Osteoporos Int. 2013;24:2275-81 pubmed publisher
    ..Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS...
  62. Chen L, Lee J, Chou C, Nair A, Battistone M, Paunescu T, et al. Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq. Proc Natl Acad Sci U S A. 2017;114:E9989-E9998 pubmed publisher
    ..In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., Notch2 chiefly in PCs vs. Jag1 chiefly in ICs), suggesting signaling cross-talk among the three cell types...
  63. Yu J, Zanotti S, Walia B, JELLISON E, Sanjay A, Canalis E. The Hajdu Cheney Mutation Is a Determinant of B-Cell Allocation of the Splenic Marginal Zone. Am J Pathol. 2018;188:149-159 pubmed publisher
    The neurogenic locus notch homolog protein (Notch)-2 receptor is a determinant of B-cell allocation, and gain-of-NOTCH2-function mutations are associated with Hajdu-Cheney syndrome (HCS), a disease presenting with osteoporosis and acro-..
  64. Almodóvar K, Iams W, Meador C, Zhao Z, York S, Horn L, et al. Longitudinal Cell-Free DNA Analysis in Patients with Small Cell Lung Cancer Reveals Dynamic Insights into Treatment Efficacy and Disease Relapse. J Thorac Oncol. 2018;13:112-123 pubmed publisher
    ..1 gene (RB1), BRAF, KIT proto-oncogene receptor tyrosine kinase gene (KIT), notch 1 gene (NOTCH1), notch 2 gene (NOTCH2), notch 3 gene (NOTCH3), notch 4 gene (NOTCH4), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit ..
  65. Hsieh J, Nofziger D, Weinmaster G, Hayward S. Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks differentiation. J Virol. 1997;71:1938-45 pubmed
    ..However, Notch2 is the predominant form expressed in spleen...
  66. Wu W, Zhang R, Shi X, Yi C, Xu L, Liu C. Notch2 is a crucial regulator of self-renewal and tumorigenicity in human hepatocellular carcinoma cells. Oncol Rep. 2016;36:181-8 pubmed publisher
    The Notch pathway plays an important role in both stem cell biology and cancer. Notch2 was reported to be upregulated in human hepatocellular carcinoma (HCC) tissues...
  67. Grisanti L, Revenkova E, Gordon R, Iomini C. Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway. Development. 2016;143:2160-71 pubmed publisher
    ..Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced...
  68. Benetkiewicz M, Idbaih A, Cousin P, Boisselier B, Marie Y, Criniere E, et al. NOTCH2 is neither rearranged nor mutated in t(1;19) positive oligodendrogliomas. PLoS ONE. 2009;4:e4107 pubmed publisher
    ..Recent studies of 1p/19q co-deleted OD suggest that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be involved in this rearrangement...
  69. Nutsch K, Chai J, Ai T, Russler Germain E, Feehley T, Nagler C, et al. Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery. Cell Rep. 2016;17:206-220 pubmed publisher
    ..Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection...
  70. Sun S, Du R, Gao J, Ning X, Xie H, Lin X, et al. Expression and clinical significance of Notch receptors in human renal cell carcinoma. Pathology. 2009;41:335-41 pubmed publisher
    ..The levels of expression of Notch2 and Notch3 were minimally detected in tumours and non-neoplastic tissues...
  71. Mu Y, Zhang X, Fan W, Li X, Chen G, Chen J, et al. [Mechanism of Astragaloside prevents cholestatic liver fibrosis through inhibition of Notch signaling activation]. Zhonghua Gan Zang Bing Za Zhi. 2017;25:575-582 pubmed publisher
    ..Results indicate that AS may be a potential treatment for cholestatic liver disease...
  72. Martin B, Ivanova M, Sarukhanov A, Kim A, Power P, Pugash D, et al. Prenatal and postnatal findings in serpentine fibula polycystic kidney syndrome and a review of the NOTCH2 spectrum disorders. Am J Med Genet A. 2014;164A:2490-5 pubmed publisher
    ..All three syndromes result from mutations in the gene that encodes NOTCH2, one of the receptors involved in Notch signaling...
  73. Mosquera J, Sboner A, Zhang L, Chen C, Sung Y, Chen H, et al. Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. Genes Chromosomes Cancer. 2013;52:1075-87 pubmed publisher
    ..A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1...
  74. Poe J, Jia W, Su H, Anand S, Rose J, Tata P, et al. An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD. Blood. 2017;130:2131-2145 pubmed publisher
    ..To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells...
  75. Tang Y, Urs S, Liaw L. Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. Circ Res. 2008;102:661-8 pubmed publisher
    ..Using primary human smooth muscle cells, we show that expression of the constitutive active ICD of human Notch1, Notch2, or Notch4 receptors increase SMA levels...
  76. Rong H, Shen H, Xu Y, Yang H. Notch signalling suppresses regulatory T-cell function in murine experimental autoimmune uveitis. Immunology. 2016;149:447-459 pubmed publisher
    ..Taken together, Notch signalling negatively modulates the immunosuppressive function of infiltrating Treg cells in mouse EAU. ..
  77. Niranjan T, Bielesz B, Gruenwald A, Ponda M, Kopp J, Thomas D, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008;14:290-8 pubmed publisher
    ..Collectively, our observations suggest that Notch activation in mature podocytes is a new mechanism in the pathogenesis of glomerular disease and thus could represent a new therapeutic target. ..
  78. Huang S, Zhao Z, Weng G, He X, Wu C, Fu C, et al. Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme. Biochem Biophys Res Commun. 2017;486:1129-1136 pubmed publisher
    ..that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells...
  79. Cheng J, Ye F, Dan G, Zhao Y, Zhao J, Zou Z. Formation and degradation of nitrogen mustard-induced MGMT-DNA crosslinking in 16HBE cells. Toxicology. 2017;389:67-73 pubmed publisher
    N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (..
  80. Wang D, Xu J, Liu B, He X, Zhou L, Hu X, et al. IL6 blockade potentiates the anti-tumor effects of ?-secretase inhibitors in Notch3-expressing breast cancer. Cell Death Differ. 2017;: pubmed publisher
    Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes...
  81. Yu W, Jiang D, Yu S, Fu J, Li Z, Wu Y, et al. SALL4 promotes osteoblast differentiation by deactivating NOTCH2 signaling. Biomed Pharmacother. 2018;98:9-17 pubmed publisher
    ..Finally, the connection and interaction between SALL4 and NOTCH2 were studied...