Genomes and Genes
Summary: A notch receptor that interacts with a variety of ligands and regulates SIGNAL TRANSDUCTION PATHWAYS for multiple cellular processes. It is widely expressed during EMBRYOGENESIS and is essential for EMBRYONIC DEVELOPMENT.
- Gordon W, Vardar Ulu D, L Heureux S, Ashworth T, Malecki M, Sanchez Irizarry C, et al. Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2. PLoS ONE. 2009;4:e6613 pubmed publisher..These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage. ..
- Rizzo P, Miao H, D Souza G, Osipo C, Song L, Yun J, et al. Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68:5226-35 pubmed publisher..Our data indicate that combinations of antiestrogens and Notch inhibitors may be effective in ERalpha(+) breast cancers and that Notch signaling is a potential therapeutic target in ERalpha(-) breast cancers...
- Mullendore M, Koorstra J, Li Y, Offerhaus G, Fan X, Henderson C, et al. Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res. 2009;15:2291-301 pubmed publisher..Our studies confirm that Notch activation is almost always ligand dependent in pancreatic cancer, and inhibition of Notch signaling is a promising therapeutic strategy in this malignancy. ..
- Palomero T, Sulis M, Cortina M, Real P, Barnes K, Ciofani M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 2007;13:1203-10 pubmed
- Gordon W, Roy M, Vardar Ulu D, Garfinkel M, Mansour M, Aster J, et al. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood. 2009;113:4381-90 pubmed publisher..The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation. ..
- Tkatchenko T, Moreno Rodriguez R, Conway S, Molkentin J, Markwald R, Tkatchenko A. Lack of periostin leads to suppression of Notch1 signaling and calcific aortic valve disease. Physiol Genomics. 2009;39:160-8 pubmed publisher..These results establish periostin as a key regulator of OFT endocardial cushion mesenchymal cell fate during embryonic development. ..
- Serneels L, Van Biervliet J, Craessaerts K, Dejaegere T, Horré K, Van Houtvin T, et al. gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease. Science. 2009;324:639-42 pubmed publisher..The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease. ..
- Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, et al. Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest. 2010;120:4040-54 pubmed publisher..In summary, our experiments establish that epithelial injury and Notch signaling play key roles in fibrosis development and indicate that Notch blockade may be a therapeutic strategy to reduce fibrosis and ESRD development. ..
- Siar C, Nakano K, Ng K, Tomida M, Nagatsuka H, Kawakami T. Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1. Eur J Med Res. 2010;15:180-4 pubmed..Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2. Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT. ..
- Westhoff B, Colaluca I, D ario G, Donzelli M, Tosoni D, Volorio S, et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci U S A. 2009;106:22293-8 pubmed publisher..Our results show that the deregulation of the Notch pathway is a relatively frequent event in NSCLCs and suggest that it might represent a possible target for molecular therapies in these tumors. ..
- Guo X, Zhou M, Ren L, Yang M, Huang S, Xu W. Small interfering RNA-mediated knockdown of Notch1 in lung. Chin Med J (Engl). 2009;122:2647-51 pubmed..72 +/- 4.24) pg/ml vs (39.79 +/- 4.09) pg/ml protein, P < 0.05). This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Th1/Th2 differentiation. ..
- Del Duca D, Wong G, Trieu P, Rodaros D, Kouremenos A, Tadevosyan A, et al. Association of neonatal hypoxia with lasting changes in left ventricular gene expression: an animal model. J Thorac Cardiovasc Surg. 2009;138:538-46, 546.e1 pubmed publisher..7% +/- 13.3% vs 85.0% +/- 2.9%, P = .024). Neonatal hypoxia is associated with significant changes in left ventricular gene expression in both neonatal and adult rats. This may have physiologic implications for the adult myocardium. ..
- Cho O, Shin H, Miele L, Golde T, Fauq A, Minter L, et al. Notch regulates cytolytic effector function in CD8+ T cells. J Immunol. 2009;182:3380-9 pubmed publisher..By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B. ..
- Silva A, Jotta P, Silveira A, Ribeiro D, Brandalise S, Yunes J, et al. Regulation of PTEN by CK2 and Notch1 in primary T-cell acute lymphoblastic leukemia: rationale for combined use of CK2- and gamma-secretase inhibitors. Haematologica. 2010;95:674-8 pubmed publisher..Our data suggest that combined use of gamma-secretase and CK2 inhibitors may have therapeutic potential in T-ALL. ..
- Xu J, Yun X, Jiang J, Wei Y, Wu Y, Zhang W, et al. Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage. Hepatology. 2010;52:142-54 pubmed publisher..The correlation of inhibited Psen1-dependent Notch1 signaling and blunted senescence-like growth arrest was also observed in HBV-associated HCC patient tumor samples...
- Tetzlaff M, Yu W, Li M, Zhang P, Finegold M, Mahon K, et al. Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci U S A. 2004;101:3338-45 pubmed..These data suggest essential functions for Fbw7 in controlling cyclin E and Notch signaling pathways in the mouse. ..
- Saint Just Ribeiro M, Hansson M, Lindberg M, Popko Scibor A, Wallberg A. GSK3beta is a negative regulator of the transcriptional coactivator MAML1. Nucleic Acids Res. 2009;37:6691-700 pubmed publisher..Finally, MAML1 translocates GSK3beta to nuclear bodies; this function requires full-length MAML1 protein. ..
- Woo H, Park J, Gwon A, Arumugam T, Jo D. Alzheimer's disease and Notch signaling. Biochem Biophys Res Commun. 2009;390:1093-7 pubmed publisher..Therefore, detailed and precise study of Notch signaling in AD is important for elucidating diverse mechanisms of pathogenesis and potentially for treating and preventing Alzheimer's disease. ..
- Garg V, Muth A, Ransom J, Schluterman M, Barnes R, King I, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270-4 pubmed..These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease. ..
- Umka J, Mustafa S, ElBeltagy M, Thorpe A, Latif L, Bennett G, et al. Valproic acid reduces spatial working memory and cell proliferation in the hippocampus. Neuroscience. 2010;166:15-22 pubmed publisher..These results support the idea that VPA may cause cognitive impairment and provide a possible mechanism for this by reducing neurogenesis within the hippocampus. ..
- Li H, Chang Y, Mohan K, Su H, Ricupero C, Baridi A, et al. Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen. Glia. 2008;56:646-58 pubmed publisher..The combined results indicate that persistent expression of activated Notch1 maintains the phenotype of radial glial cells, inhibits their differentiation, and promotes their adhesion and migration on a laminin/nidogen complex. ..
- Kohlhof H, Hampel F, Hoffmann R, Burtscher H, Weidle U, H lzel M, et al. Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells. Blood. 2009;113:5506-15 pubmed publisher..These findings suggest that Notch signaling in B cells and B-cell lymphomas is only compatible with proliferation if pathways leading to antiapototic signals are active...
- Ito T, Kwon H, Zimdahl B, Congdon K, Blum J, Lento W, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010;466:765-8 pubmed publisher..These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias...
- Hanlon L, Avila J, Demarest R, Troutman S, Allen M, Ratti F, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 2010;70:4280-6 pubmed publisher..Unexpectedly, the loss of Notch1 in this model resulted in increased tumor incidence and progression, implying that Notch1 can function as a tumor suppressor gene in PDAC. ..
- Jiao Z, Wang W, Guo M, Zhang T, Chen L, Wang Y, et al. Expression analysis of Notch-related molecules in peripheral blood T helper cells of patients with rheumatoid arthritis. Scand J Rheumatol. 2010;39:26-32 pubmed publisher..The present study demonstrated that T helper cells from RA patients display a significantly altered expression profile of Notch receptors and enhanced activation of Notch signalling compared with HC. ..
- Asnafi V, Buzyn A, Le Noir S, Baleydier F, Simon A, Beldjord K, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood. 2009;113:3918-24 pubmed publisher..01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL. ..
- Chen J, Cui X, Zacharek A, Ding G, Shehadah A, Jiang Q, et al. Niaspan treatment increases tumor necrosis factor-alpha-converting enzyme and promotes arteriogenesis after stroke. J Cereb Blood Flow Metab. 2009;29:911-20 pubmed publisher..Knockdown of Notch1 marginally decreased arterial sprouting and VSMC migration compared with scrambled control. Niaspan promotes arteriogenesis, which is mediated, in part, by TACE. ..
- Bin Hafeez B, Adhami V, Asim M, Siddiqui I, Bhat K, Zhong W, et al. Targeted knockdown of Notch1 inhibits invasion of human prostate cancer cells concomitant with inhibition of matrix metalloproteinase-9 and urokinase plasminogen activator. Clin Cancer Res. 2009;15:452-9 pubmed publisher..Thus, targeting of Notch1 could be an effective therapeutic approach against PCa. ..
- Casey L, Lan Y, Cho E, Maltby K, Gridley T, Jiang R. Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development. Dev Dyn. 2006;235:1830-44 pubmed
- Zhao N, Guo Y, Zhang M, Lin L, Zheng Z. Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. Oncol Rep. 2010;23:1443-7 pubmed..This also suggests a molecular mechanism for the inhibitory effect of Notch-1 RNA interference on glioma cell proliferation through Akt-mTOR signaling pathway. ..
- Kapoor N, Narayana Y, Patil S, Balaji K. Nitric oxide is involved in Mycobacterium bovis bacillus Calmette-Guérin-activated Jagged1 and Notch1 signaling. J Immunol. 2010;184:3117-26 pubmed publisher..These findings provide new insights into mechanisms by which Notch1, TLR2, and NO signals are integrated in a cross talk that modulates a defined set of effector functions in macrophages. ..
- Sörensen I, Adams R, Gossler A. DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood. 2009;113:5680-8 pubmed publisher..Our results establish DLL1 as a critical endothelial Notch ligand required for maintaining arterial identity during mouse fetal development and suggest context-dependent interrelations of the VEGFA and Notch signaling pathways. ..
- Liu R, Li X, Tulpule A, Zhou Y, Scehnet J, Zhang S, et al. KSHV-induced notch components render endothelial and mural cell characteristics and cell survival. Blood. 2010;115:887-95 pubmed publisher..Soluble Dll4 was also highly active in vivo against KS tumor xenograft. It inhibited tumor cell growth, induced tumor cell death, and reduced vessel perfusion. Soluble Dll4 is thus a candidate for clinical investigation. ..
- Whitworth G, Zandberg W, Clark T, Vocadlo D. Mammalian Notch is modified by D-Xyl-alpha1-3-D-Xyl-alpha1-3-D-Glc-beta1-O-Ser: implementation of a method to study O-glucosylation. Glycobiology. 2010;20:287-99 pubmed publisher..Wider application of this approach should facilitate identification of other EGF-containing proteins bearing this O-glycan and aid in their study. ..
- Wells J, Lee B, Cai A, Karapetyan A, Lee W, Rugg E, et al. Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1. J Biol Chem. 2009;284:29125-35 pubmed publisher..These findings shed light on how an epidermal cell maintains a proliferation-competent and differentiation-resistant state. ..
- Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, et al. Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol. 2010;184:4673-8 pubmed publisher..These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses. ..
- Murphy P, Lu G, Shiah S, Bollen A, Wang R. Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease. Lab Invest. 2009;89:971-82 pubmed publisher..We then analyzed receptor activity using an antibody to the activated form of the Notch1 receptor, and found increased levels of activity...
- Acharyya S, Sharma S, Cheng A, Ladner K, He W, Kline W, et al. TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy. PLoS ONE. 2010;5:e12479 pubmed publisher..This regulation coincides with elevated levels of muscle derived TNFalpha that is also under IKKbeta and NF-kappaB control...
- Hunter N, Dymecki S. Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus. Development. 2007;134:3449-60 pubmed
- Ma D, Dai J, Zhu X, Yan S, Zhao P, Zhang J, et al. Aberrant expression of Notch signaling molecules in patients with immune thrombocytopenic purpura. Ann Hematol. 2010;89:155-61 pubmed publisher..Our findings suggest that the aberrant expression profile of Notch pathway may be involved in ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept. ..
- Luna Zurita L, Prados B, Grego Bessa J, Luxan G, del Monte G, Benguria A, et al. Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation. J Clin Invest. 2010;120:3493-507 pubmed publisher..This embryonic Notch1-Bmp2-Snail1 relationship may be relevant in adult valve disease, in which decreased NOTCH signaling causes valve mesenchyme cell formation, fibrosis, and calcification. ..
- Ambler C, Watt F. Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1. Development. 2010;137:3569-79 pubmed publisher..We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin...
- Yeh T, Wu C, Hsu K, Liao W, Yang M, Li A, et al. The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res. 2009;69:5039-48 pubmed publisher..The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and ..
- Henley B, McDermott K. The expression of neuroepithelial cell fate determinants in rat spinal cord development. J Mol Neurosci. 2010;42:28-34 pubmed publisher..By understanding how neural stem cells are regulated in spinal cord development in vivo, we may gain insight of relevance to cell replacement strategies to treat spinal cord injuries. ..
- Wang M, Wu L, Wang L, Xin X. Down-regulation of Notch1 by gamma-secretase inhibition contributes to cell growth inhibition and apoptosis in ovarian cancer cells A2780. Biochem Biophys Res Commun. 2010;393:144-9 pubmed publisher..These findings also support the conclusion that blocking of the Notch1 activity by gamma-secretase inhibitors represents a potentially attractive strategy of targeted therapy for ovarian cancer. ..
- Yamada S, Hotta K, Yamamoto T, Ueno N, Satoh N, Takahashi H. Interaction of notochord-derived fibrinogen-like protein with Notch regulates the patterning of the central nervous system of Ciona intestinalis embryos. Dev Biol. 2009;328:1-12 pubmed publisher..Therefore, it is highly likely that the interaction between the notochord-based fibrinogen-like protein and the neural tube-based Notch signaling plays an essential role in the proper patterning of CNS...
- Liu Z, Teng L, Bailey S, Frost A, Bland K, LoBuglio A, et al. Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling. Cancer Biol Ther. 2009;8:1840-51 pubmed..These results suggest that KLF4 could contribute to breast tumor progression by activating synthesis of Notch1 and by promoting signaling through a non-canonical Notch1 pathway. ..
- Fujita H, Ohuchida K, Mizumoto K, Egami T, Miyoshi K, Moriyama T, et al. Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells. Cancer Sci. 2009;100:2309-17 pubmed publisher..Direct cell contact between cancer cells and PSCs plays an important role in the control of cancer cell proliferation, and is essential to the understanding of tumor-stromal interactions. ..
- Sibbe M, Forster E, Basak O, Taylor V, Frotscher M. Reelin and Notch1 cooperate in the development of the dentate gyrus. J Neurosci. 2009;29:8578-85 pubmed publisher..These results suggest that Reelin enhances Notch1 signaling, thereby contributing to the formation of the radial glial scaffold and the normal development of the dentate gyrus. ..
- Bienvenu F, Jirawatnotai S, Elias J, Meyer C, Mizeracka K, Marson A, et al. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature. 2010;463:374-8 pubmed publisher..Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein. ..
- Buonamici S, Trimarchi T, Ruocco M, Reavie L, Cathelin S, Mar B, et al. CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature. 2009;459:1000-4 pubmed publisher..Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications. ..
- Mazur P, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2010;107:13438-43 pubmed publisher..Our study supports the concept of distinctive roles of individual Notch receptors in cancer development. ..
- Corada M, Nyqvist D, Orsenigo F, Caprini A, Giampietro C, Taketo M, et al. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell. 2010;18:938-49 pubmed publisher..We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification. ..