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A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition.

Cordle J, Johnson S, Tay JZ, Roversi P, Wilkin MB, de Madrid BH, Shimizu H, Jensen S, Whiteman P, Jin B, Redfield C, Baron M, Lea SM, Handford PA
Nat Struct Mol Biol 15 849-57 (2008)
Cited: 160 times
EuropePMC logo PMID: 18660822

Abstract

The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1(DSL-EGF3)). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor.

Reviews - 2vj3 mentioned but not cited (4)

  1. The canonical Notch signaling pathway: unfolding the activation mechanism. Kopan R, Ilagan MX. Cell 137 216-233 (2009)
  2. The molecular logic of Notch signaling--a structural and biochemical perspective. Gordon WR, Arnett KL, Blacklow SC. J Cell Sci 121 3109-3119 (2008)
  3. Notch receptor-ligand binding and activation: insights from molecular studies. Chillakuri CR, Sheppard D, Lea SM, Handford PA. Semin Cell Dev Biol 23 421-428 (2012)
  4. Significance of glycosylation in Notch signaling. Takeuchi H, Haltiwanger RS. Biochem Biophys Res Commun 453 235-242 (2014)

Articles - 2vj3 mentioned but not cited (25)

  1. Somatic mutant clones colonize the human esophagus with age. Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F, Hall MWJ, Cagan A, Murai K, Mahbubani K, Stratton MR, Fitzgerald RC, Handford PA, Campbell PJ, Saeb-Parsy K, Jones PH. Science 362 911-917 (2018)
  2. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Wang NJ, Sanborn Z, Arnett KL, Bayston LJ, Liao W, Proby CM, Leigh IM, Collisson EA, Gordon PB, Jakkula L, Pennypacker S, Zou Y, Sharma M, North JP, Vemula SS, Mauro TM, Neuhaus IM, Leboit PE, Hur JS, Park K, Huh N, Kwok PY, Arron ST, Massion PP, Bale AE, Haussler D, Cleaver JE, Gray JW, Spellman PT, South AP, Aster JC, Blacklow SC, Cho RJ. Proc Natl Acad Sci U S A 108 17761-17766 (2011)
  3. Integrated genomic characterization of IDH1-mutant glioma malignant progression. Bai H, Harmancı AS, Erson-Omay EZ, Li J, Coşkun S, Simon M, Krischek B, Özduman K, Omay SB, Sorensen EA, Turcan Ş, Bakırcığlu M, Carrión-Grant G, Murray PB, Clark VE, Ercan-Sencicek AG, Knight J, Sencar L, Altınok S, Kaulen LD, Gülez B, Timmer M, Schramm J, Mishra-Gorur K, Henegariu O, Moliterno J, Louvi A, Chan TA, Tannheimer SL, Pamir MN, Vortmeyer AO, Bilguvar K, Yasuno K, Günel M. Nat Genet 48 59-66 (2016)
  4. A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. Cordle J, Johnson S, Tay JZ, Roversi P, Wilkin MB, de Madrid BH, Shimizu H, Jensen S, Whiteman P, Jin B, Redfield C, Baron M, Lea SM, Handford PA. Nat Struct Mol Biol 15 849-857 (2008)
  5. Mutations in NOTCH1 cause Adams-Oliver syndrome. Stittrich AB, Lehman A, Bodian DL, Ashworth J, Zong Z, Li H, Lam P, Khromykh A, Iyer RK, Vockley JG, Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE, Roach JC, Patel MS. Am J Hum Genet 95 275-284 (2014)
  6. Fringe-mediated extension of O-linked fucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands. Taylor P, Takeuchi H, Sheppard D, Chillakuri C, Lea SM, Haltiwanger RS, Handford PA. Proc Natl Acad Sci U S A 111 7290-7295 (2014)
  7. Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies. Southgate L, Sukalo M, Karountzos ASV, Taylor EJ, Collinson CS, Ruddy D, Snape KM, Dallapiccola B, Tolmie JL, Joss S, Brancati F, Digilio MC, Graul-Neumann LM, Salviati L, Coerdt W, Jacquemin E, Wuyts W, Zenker M, Machado RD, Trembath RC. Circ Cardiovasc Genet 8 572-581 (2015)
  8. Structural insights into the mechanism of protein O-fucosylation. Lira-Navarrete E, Valero-González J, Villanueva R, Martínez-Júlvez M, Tejero T, Merino P, Panjikar S, Hurtado-Guerrero R. PLoS One 6 e25365 (2011)
  9. Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site. Fowler JC, King C, Bryant C, Hall MWJ, Sood R, Ong SH, Earp E, Fernandez-Antoran D, Koeppel J, Dentro SC, Shorthouse D, Durrani A, Fife K, Rytina E, Milne D, Roshan A, Mahububani K, Saeb-Parsy K, Hall BA, Gerstung M, Jones PH. Cancer Discov 11 340-361 (2021)
  10. Mussel adhesion is dictated by time-regulated secretion and molecular conformation of mussel adhesive proteins. Petrone L, Kumar A, Sutanto CN, Patil NJ, Kannan S, Palaniappan A, Amini S, Zappone B, Verma C, Miserez A. Nat Commun 6 8737 (2015)
  11. Targeting specific regions of the Notch3 ligand-binding domain induces apoptosis and inhibits tumor growth in lung cancer. Lin L, Mernaugh R, Yi F, Blum D, Carbone DP, Dang TP. Cancer Res 70 632-638 (2010)
  12. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Yu H, Takeuchi M, LeBarron J, Kantharia J, London E, Bakker H, Haltiwanger RS, Li H, Takeuchi H. Nat Chem Biol 11 847-854 (2015)
  13. The RGD finger of Del-1 is a unique structural feature critical for integrin binding. Schürpf T, Chen Q, Liu JH, Wang R, Springer TA, Wang JH. FASEB J 26 3412-3420 (2012)
  14. Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands. Suckling RJ, Korona B, Whiteman P, Chillakuri C, Holt L, Handford PA, Lea SM. EMBO J 36 2204-2215 (2017)
  15. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia. Ye Q, Jiang J, Zhan G, Yan W, Huang L, Hu Y, Su H, Tong Q, Yue M, Li H, Yao G, Zhang Y, Liu H. Sci Rep 6 26510 (2016)
  16. Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Yu H, Takeuchi H, Takeuchi M, Liu Q, Kantharia J, Haltiwanger RS, Li H. Nat Chem Biol 12 735-740 (2016)
  17. Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies. Weisshuhn PC, Sheppard D, Taylor P, Whiteman P, Lea SM, Handford PA, Redfield C. Structure 24 555-566 (2016)
  18. Molecular basis for Jagged-1/Serrate ligand recognition by the Notch receptor. Whiteman P, de Madrid BH, Taylor P, Li D, Heslop R, Viticheep N, Tan JZ, Shimizu H, Callaghan J, Masiero M, Li JL, Banham AH, Harris AL, Lea SM, Redfield C, Baron M, Handford PA. J Biol Chem 288 7305-7312 (2013)
  19. Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development. Liu YF, Chiang SL, Lin CY, Chang JG, Chung CM, Ko AM, Lin YZ, Lee CH, Lee KW, Chen MK, Hua CH, Tsai MH, Chen YC, Ko YC. Sci Rep 6 24014 (2016)
  20. A series of Notch3 mutations in CADASIL; insights from 3D molecular modelling and evolutionary analyses. Vlachakis D, Tsaniras SC, Ioannidou K, Papageorgiou L, Baumann M, Kossida S. J Mol Biochem 3 134 (2014)
  21. Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening. Platonova N, Parravicini C, Sensi C, Paoli A, Colombo M, Neri A, Eberini I, Chiaramonte R. PLoS One 12 e0182640 (2017)
  22. NMR spectroscopic and bioinformatic analyses of the LTBP1 C-terminus reveal a highly dynamic domain organisation. Robertson IB, Handford PA, Redfield C. PLoS One 9 e87125 (2014)
  23. Mutations observed in somatic evolution reveal underlying gene mechanisms. Hall MWJ, Shorthouse D, Alcraft R, Jones PH, Hall BA. Commun Biol 6 753 (2023)
  24. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  25. Molecular docking analysis of phytocompounds from Andrographis paniculata binding with proteins in the notch-signaling pathway. Deiva Suga SS, Krishna Mohan S, Sreekandan RN, K M, Kamaraj D, Veeraraghavan VP, Jayaraman S, Rajagopal P. Bioinformation 16 923-928 (2020)


Reviews citing this publication (41)

  1. Notch signalling in context. Bray SJ. Nat Rev Mol Cell Biol 17 722-735 (2016)
  2. The Notch signalling system: recent insights into the complexity of a conserved pathway. Guruharsha KG, Kankel MW, Artavanis-Tsakonas S. Nat Rev Genet 13 654-666 (2012)
  3. Therapeutic modulation of Notch signalling--are we there yet? Andersson ER, Lendahl U. Nat Rev Drug Discov 13 357-378 (2014)
  4. Targeting Notch to target cancer stem cells. Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, Miele L. Clin Cancer Res 16 3141-3152 (2010)
  5. The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force. Kovall RA, Gebelein B, Sprinzak D, Kopan R. Dev Cell 41 228-241 (2017)
  6. Canonical and non-canonical Notch ligands. D'Souza B, Meloty-Kapella L, Weinmaster G. Curr Top Dev Biol 92 73-129 (2010)
  7. Mechanism and significance of cis-inhibition in Notch signalling. del Álamo D, Rouault H, Schweisguth F. Curr Biol 21 R40-7 (2011)
  8. Role of Notch and its oncogenic signaling crosstalk in breast cancer. Guo S, Liu M, Gonzalez-Perez RR. Biochim Biophys Acta 1815 197-213 (2011)
  9. Functions of notch signaling in the immune system: consensus and controversies. Yuan JS, Kousis PC, Suliman S, Visan I, Guidos CJ. Annu Rev Immunol 28 343-365 (2010)
  10. The notch ligand JAGGED1 as a target for anti-tumor therapy. Li D, Masiero M, Banham AH, Harris AL. Front Oncol 4 254 (2014)
  11. Stochastic mechanisms of cell fate specification that yield random or robust outcomes. Johnston RJ, Desplan C. Annu Rev Cell Dev Biol 26 689-719 (2010)
  12. Biophysics of Notch Signaling. Sprinzak D, Blacklow SC. Annu Rev Biophys 50 157-189 (2021)
  13. Notching on Cancer's Door: Notch Signaling in Brain Tumors. Teodorczyk M, Schmidt MHH. Front Oncol 4 341 (2014)
  14. Dissecting the fibrillin microfibril: structural insights into organization and function. Jensen SA, Robertson IB, Handford PA. Structure 20 215-225 (2012)
  15. Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'. Rich RL, Myszka DG. J Mol Recognit 23 1-64 (2010)
  16. Role of glycosylation of Notch in development. Takeuchi H, Haltiwanger RS. Semin Cell Dev Biol 21 638-645 (2010)
  17. Spermatogenesis-defective (spe) mutants of the nematode Caenorhabditis elegans provide clues to solve the puzzle of male germline functions during reproduction. Nishimura H, L'Hernault SW. Dev Dyn 239 1502-1514 (2010)
  18. Structural basis for recognition of cellular and viral ligands by NK cell receptors. Li Y, Mariuzza RA. Front Immunol 5 123 (2014)
  19. Role of unusual O-glycans in intercellular signaling. Luther KB, Haltiwanger RS. Int J Biochem Cell Biol 41 1011-1024 (2009)
  20. Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells. Zhou W, Wang G, Guo S. Biochim Biophys Acta 1836 304-320 (2013)
  21. Cis-trans interactions of cell surface receptors: biological roles and structural basis. Held W, Mariuzza RA. Cell Mol Life Sci 68 3469-3478 (2011)
  22. Notch: Implications of endogenous inhibitors for therapy. Dikic I, Schmidt MHH. Bioessays 32 481-487 (2010)
  23. Phosphorylation-dependent regulation of Notch1 signaling: the fulcrum of Notch1 signaling. Lee HJ, Kim MY, Park HS. BMB Rep 48 431-437 (2015)
  24. Notch Signaling in B Cell Immune Responses. Garis M, Garrett-Sinha LA. Front Immunol 11 609324 (2020)
  25. Targeting Notch signaling cross-talk with estrogen receptor and ErbB-2 in breast cancer. Rizzo P, Osipo C, Pannuti A, Golde T, Osborne B, Miele L. Adv Enzyme Regul 49 134-141 (2009)
  26. Current Challenges in Translating Tissue-Engineered Heart Valves. Stassen OMJA, Muylaert DEP, Bouten CVC, Hjortnaes J. Curr Treat Options Cardiovasc Med 19 71 (2017)
  27. Glycosylated Notch and Cancer. Pakkiriswami S, Couto A, Nagarajan U, Georgiou M. Front Oncol 6 37 (2016)
  28. The Notch signaling pathway in skeletal muscle health and disease. Vargas-Franco D, Kalra R, Draper I, Pacak CA, Asakura A, Kang PB. Muscle Nerve 66 530-544 (2022)
  29. Current Views on the Roles of O-Glycosylation in Controlling Notch-Ligand Interactions. Saiki W, Ma C, Okajima T, Takeuchi H. Biomolecules 11 309 (2021)
  30. Evolving Roles of Notch Signaling in Cortical Development. Nian FS, Hou PS. Front Neurosci 16 844410 (2022)
  31. The role of Notch in patterning the human vertebral column. Dunwoodie SL. Curr Opin Genet Dev 19 329-337 (2009)
  32. Role of notch signaling in osteoimmunology--from the standpoint of osteoclast differentiation. Duan L, Ren Y. Eur J Orthod 35 175-182 (2013)
  33. Making sense out of missense mutations: Mechanistic dissection of Notch receptors through structure-function studies in Drosophila. Yamamoto S. Dev Growth Differ 62 15-34 (2020)
  34. Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation. O'Brien KA, Murray AJ, Simonson TS. Life (Basel) 12 437 (2022)
  35. Notch-Mediated Cell Adhesion. Murata A, Hayashi S. Biology (Basel) 5 E5 (2016)
  36. Principal signalling complexes in haematopoiesis: structural aspects and mimetic discovery. Tarasova A, Haylock D, Winkler D. Cytokine Growth Factor Rev 22 231-253 (2011)
  37. To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis. Ng HL, Quail E, Cruickshank MN, Ulgiati D. Biomolecules 11 849 (2021)
  38. New tricks for an old pathway: emerging Notch-based biotechnologies and therapeutics. Medina E, Perez DH, Antfolk D, Luca VC. Trends Pharmacol Sci 44 934-948 (2023)
  39. Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy. Wang S, Gu S, Chen J, Yuan Z, Liang P, Cui H. Biomolecules 14 480 (2024)
  40. Progression of Notch signaling regulation of B cells under radiation exposure. Shu X, Wang J, Zeng H, Shao L. Front Immunol 15 1339977 (2024)
  41. Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders. Kałafut J, Czerwonka A, Czapla K, Przybyszewska-Podstawka A, Hermanowicz JM, Rivero-Müller A, Borkiewicz L. Int J Mol Sci 24 12579 (2023)

Articles citing this publication (90)

  1. Cis-interactions between Notch and Delta generate mutually exclusive signalling states. Sprinzak D, Lakhanpal A, Lebon L, Santat LA, Fontes ME, Anderson GA, Garcia-Ojalvo J, Elowitz MB. Nature 465 86-90 (2010)
  2. Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Luca VC, Kim BC, Ge C, Kakuda S, Wu D, Roein-Peikar M, Haltiwanger RS, Zhu C, Ha T, Garcia KC. Science 355 1320-1324 (2017)
  3. Structural biology. Structural basis for Notch1 engagement of Delta-like 4. Luca VC, Jude KM, Pierce NW, Nachury MV, Fischer S, Garcia KC. Science 347 847-853 (2015)
  4. The CD46-Jagged1 interaction is critical for human TH1 immunity. Le Friec G, Sheppard D, Whiteman P, Karsten CM, Shamoun SA, Laing A, Bugeon L, Dallman MJ, Melchionna T, Chillakuri C, Smith RA, Drouet C, Couzi L, Fremeaux-Bacchi V, Köhl J, Waddington SN, McDonnell JM, Baker A, Handford PA, Lea SM, Kemper C. Nat Immunol 13 1213-1221 (2012)
  5. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma. de Antonellis P, Medaglia C, Cusanelli E, Andolfo I, Liguori L, De Vita G, Carotenuto M, Bello A, Formiggini F, Galeone A, De Rosa G, Virgilio A, Scognamiglio I, Sciro M, Basso G, Schulte JH, Cinalli G, Iolascon A, Zollo M. PLoS One 6 e24584 (2011)
  6. Notch, IL-1 and leptin crosstalk outcome (NILCO) is critical for leptin-induced proliferation, migration and VEGF/VEGFR-2 expression in breast cancer. Guo S, Gonzalez-Perez RR. PLoS One 6 e21467 (2011)
  7. NOTCH decoys that selectively block DLL/NOTCH or JAG/NOTCH disrupt angiogenesis by unique mechanisms to inhibit tumor growth. Kangsamaksin T, Murtomaki A, Kofler NM, Cuervo H, Chaudhri RA, Tattersall IW, Rosenstiel PE, Shawber CJ, Kitajewski J. Cancer Discov 5 182-197 (2015)
  8. Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states. LeBon L, Lee TV, Sprinzak D, Jafar-Nejad H, Elowitz MB. Elife 3 e02950 (2014)
  9. cis-Inhibition of Notch by endogenous Delta biases the outcome of lateral inhibition. Miller AC, Lyons EL, Herman TG. Curr Biol 19 1378-1383 (2009)
  10. Thrombospondin 1--a key astrocyte-derived neurogenic factor. Lu Z, Kipnis J. FASEB J 24 1925-1934 (2010)
  11. Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta-like 1. Andrawes MB, Xu X, Liu H, Ficarro SB, Marto JA, Aster JC, Blacklow SC. J Biol Chem 288 25477-25489 (2013)
  12. Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. Zuniga E, Stellabotte F, Crump JG. Development 137 1843-1852 (2010)
  13. Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Bauer RC, Laney AO, Smith R, Gerfen J, Morrissette JJ, Woyciechowski S, Garbarini J, Loomes KM, Krantz ID, Urban Z, Gelb BD, Goldmuntz E, Spinner NB. Hum Mutat 31 594-601 (2010)
  14. NOTCH pathway inactivation promotes bladder cancer progression. Maraver A, Fernandez-Marcos PJ, Cash TP, Mendez-Pertuz M, Dueñas M, Maietta P, Martinelli P, Muñoz-Martin M, Martínez-Fernández M, Cañamero M, Roncador G, Martinez-Torrecuadrada JL, Grivas D, de la Pompa JL, Valencia A, Paramio JM, Real FX, Serrano M. J Clin Invest 125 824-830 (2015)
  15. O-glucose trisaccharide is present at high but variable stoichiometry at multiple sites on mouse Notch1. Rana NA, Nita-Lazar A, Takeuchi H, Kakuda S, Luther KB, Haltiwanger RS. J Biol Chem 286 31623-31637 (2011)
  16. Selective regulation of Notch ligands during angiogenesis is mediated by vimentin. Antfolk D, Sjöqvist M, Cheng F, Isoniemi K, Duran CL, Rivero-Muller A, Antila C, Niemi R, Landor S, Bouten CVC, Bayless KJ, Eriksson JE, Sahlgren CM. Proc Natl Acad Sci U S A 114 E4574-E4581 (2017)
  17. The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each other's activities. Sánchez-Solana B, Nueda ML, Ruvira MD, Ruiz-Hidalgo MJ, Monsalve EM, Rivero S, García-Ramírez JJ, Díaz-Guerra MJ, Baladrón V, Laborda J. Biochim Biophys Acta 1813 1153-1164 (2011)
  18. Cis interaction between Semaphorin6A and Plexin-A4 modulates the repulsive response to Sema6A. Haklai-Topper L, Mlechkovich G, Savariego D, Gokhman I, Yaron A. EMBO J 29 2635-2645 (2010)
  19. Common and complex Notch1 mutations in Chinese oral squamous cell carcinoma. Song X, Xia R, Li J, Long Z, Ren H, Chen W, Mao L. Clin Cancer Res 20 701-710 (2014)
  20. CADASIL mutations enhance spontaneous multimerization of NOTCH3. Opherk C, Duering M, Peters N, Karpinska A, Rosner S, Schneider E, Bader B, Giese A, Dichgans M. Hum Mol Genet 18 2761-2767 (2009)
  21. Multiple O-glucosylation sites on Notch function as a buffer against temperature-dependent loss of signaling. Leonardi J, Fernandez-Valdivia R, Li YD, Simcox AA, Jafar-Nejad H. Development 138 3569-3578 (2011)
  22. Direct observation of proteolytic cleavage at the S2 site upon forced unfolding of the Notch negative regulatory region. Stephenson NL, Avis JM. Proc Natl Acad Sci U S A 109 E2757-65 (2012)
  23. Cis-activation in the Notch signaling pathway. Nandagopal N, Santat LA, Elowitz MB. Elife 8 e37880 (2019)
  24. Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1. Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM. Nat Chem Biol 13 757-763 (2017)
  25. NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. Farah E, Li C, Cheng L, Kong Y, Lanman NA, Pascuzzi P, Lorenz GR, Zhang Y, Ahmad N, Li L, Ratliff T, Liu X. J Biol Chem 294 8543-8554 (2019)
  26. Optical tweezers studies on Notch: single-molecule interaction strength is independent of ligand endocytosis. Shergill B, Meloty-Kapella L, Musse AA, Weinmaster G, Botvinick E. Dev Cell 22 1313-1320 (2012)
  27. Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation. Dos Santos SN, Sheldon H, Pereira JX, Paluch C, Bridges EM, El-Cheikh MC, Harris AL, Bernardes ES. Oncotarget 8 49484-49501 (2017)
  28. Notch signaling promotes osteoclast maturation and resorptive activity. Ashley JW, Ahn J, Hankenson KD. J Cell Biochem 116 2598-2609 (2015)
  29. Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins. Jensen SA, Iqbal S, Lowe ED, Redfield C, Handford PA. Structure 17 759-768 (2009)
  30. A role of receptor Notch in ligand cis-inhibition in Drosophila. Becam I, Fiuza UM, Arias AM, Milán M. Curr Biol 20 554-560 (2010)
  31. An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling. Fleming RJ, Hori K, Sen A, Filloramo GV, Langer JM, Obar RA, Artavanis-Tsakonas S, Maharaj-Best AC. Development 140 2039-2049 (2013)
  32. Notch signaling in astrocytes mediates their morphological response to an inflammatory challenge. Acaz-Fonseca E, Ortiz-Rodriguez A, Azcoitia I, Garcia-Segura LM, Arevalo MA. Cell Death Discov 5 85 (2019)
  33. Substrate-dependent modulation of 3D spheroid morphology self-assembled in mesenchymal stem cell-endothelial progenitor cell coculture. Hsu SH, Ho TT, Huang NC, Yao CL, Peng LH, Dai NT. Biomaterials 35 7295-7307 (2014)
  34. Competition in notch signaling with cis enriches cell fate decisions. Formosa-Jordan P, Ibañes M. PLoS One 9 e95744 (2014)
  35. Membrane tethered delta activates notch and reveals a role for spatio-mechanical regulation of the signaling pathway. Narui Y, Salaita K. Biophys J 105 2655-2665 (2013)
  36. Structural analysis uncovers lipid-binding properties of Notch ligands. Chillakuri CR, Sheppard D, Ilagan MX, Holt LR, Abbott F, Liang S, Kopan R, Handford PA, Lea SM. Cell Rep 5 861-867 (2013)
  37. Structure of the fibrillin-1 N-terminal domains suggests that heparan sulfate regulates the early stages of microfibril assembly. Yadin DA, Robertson IB, McNaught-Davis J, Evans P, Stoddart D, Handford PA, Jensen SA, Redfield C. Structure 21 1743-1756 (2013)
  38. The microRNA pathway regulates the temporal pattern of Notch signaling in Drosophila follicle cells. Poulton JS, Huang YC, Smith L, Sun J, Leake N, Schleede J, Stevens LM, Deng WM. Development 138 1737-1745 (2011)
  39. A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells. Murata A, Okuyama K, Sakano S, Kajiki M, Hirata T, Yagita H, Zúñiga-Pflücker JC, Miyake K, Akashi-Takamura S, Moriwaki S, Niida S, Yoshino M, Hayashi S. J Immunol 185 3905-3912 (2010)
  40. One size does not fit all: navigating the multi-dimensional space to optimize T-cell engaging protein therapeutics. Chen W, Yang F, Wang C, Narula J, Pascua E, Ni I, Ding S, Deng X, Chu ML, Pham A, Jiang X, Lindquist KC, Doonan PJ, Van Blarcom T, Yeung YA, Chaparro-Riggers J. MAbs 13 1871171 (2021)
  41. The expression of Delta ligands in the sponge Amphimedon queenslandica suggests an ancient role for Notch signaling in metazoan development. Richards GS, Degnan BM. Evodevo 3 15 (2012)
  42. Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo. Preuße K, Tveriakhina L, Schuster-Gossler K, Gaspar C, Rosa AI, Henrique D, Gossler A, Stauber M. PLoS Genet 11 e1005328 (2015)
  43. Mechanisms of ligand-mediated inhibition in Notch signaling activity in Drosophila. Fiuza UM, Klein T, Martinez Arias A, Hayward P. Dev Dyn 239 798-805 (2010)
  44. Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption. Larsen C, Etzerodt A, Madsen M, Skjødt K, Moestrup SK, Andersen CBF. Nat Commun 9 5204 (2018)
  45. Development of Therapeutic Anti-JAGGED1 Antibodies for Cancer Therapy. Masiero M, Li D, Whiteman P, Bentley C, Greig J, Hassanali T, Watts S, Stribbling S, Yates J, Bealing E, Li JL, Chillakuri C, Sheppard D, Serres S, Sarmiento-Soto M, Larkin J, Larkin J, Sibson NR, Handford PA, Harris AL, Banham AH. Mol Cancer Ther 18 2030-2042 (2019)
  46. The ectodomains determine ligand function in vivo and selectivity of DLL1 and DLL4 toward NOTCH1 and NOTCH2 in vitro. Tveriakhina L, Schuster-Gossler K, Jarrett SM, Andrawes MB, Rohrbach M, Blacklow SC, Gossler A. Elife 7 e40045 (2018)
  47. NOTCH1 Mutations in Aortic Stenosis: Association with Osteoprotegerin/RANK/RANKL. Irtyuga O, Malashicheva A, Zhiduleva E, Freylikhman O, Rotar O, Bäck M, Tarnovskaya S, Kostareva A, Moiseeva O. Biomed Res Int 2017 6917907 (2017)
  48. Collagen represses canonical Notch signaling and binds to Notch ectodomain. Zhang X, Meng H, Wang MM. Int J Biochem Cell Biol 45 1274-1280 (2013)
  49. Soluble Notch ligand and receptor peptides act antagonistically during angiogenesis. Klose R, Berger C, Moll I, Adam MG, Schwarz F, Mohr K, Augustin HG, Fischer A. Cardiovasc Res 107 153-163 (2015)
  50. Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa. Ma X, Guan L, Wu W, Zhang Y, Zheng W, Gao YT, Long J, Wu N, Wu L, Xiang Y, Xu B, Shen M, Chen Y, Wang Y, Yin Y, Li Y, Xu H, Xu X, Li Y. Sci Rep 5 9236 (2015)
  51. Notch ligand delta-like1: X-ray crystal structure and binding affinity. Kershaw NJ, Church NL, Griffin MD, Luo CS, Adams TE, Burgess AW. Biochem J 468 159-166 (2015)
  52. Notch signalling: receptor cis-inhibition to achieve directionality. del Alamo D, Schweisguth F. Curr Biol 19 R683-4 (2009)
  53. Antibodies against the extracellular domain of human Notch1 receptor reveal the critical role of epidermal-growth-factor-like repeats 25-26 in ligand binding and receptor activation. Sharma A, Rangarajan A, Dighe RR. Biochem J 449 519-530 (2013)
  54. The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch activity to modulate germline stem cell niche formation. Shimizu H, Wilkin MB, Woodcock SA, Bonfini A, Hung Y, Mazaleyrat S, Baron M. Open Biol 7 160322 (2017)
  55. Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila. Xie G, Zhang H, Du G, Huang Q, Liang X, Ma J, Jiao R. PLoS One 7 e36362 (2012)
  56. Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand. Greene M, Lai Y, Pajcini K, Bailis W, Pear WS, Lancaster E. PLoS One 11 e0161157 (2016)
  57. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4. Grosche S, Marenholz I, Esparza-Gordillo J, Arnau-Soler A, Pairo-Castineira E, Rüschendorf F, Ahluwalia TS, Almqvist C, Arnold A, Australian Asthma Genetics Consortium (AAGC), Baurecht H, Bisgaard H, Bønnelykke K, Brown SJ, Bustamante M, Curtin JA, Custovic A, Dharmage SC, Esplugues A, Falchi M, Fernandez-Orth D, Ferreira MAR, Franke A, Gerdes S, Gieger C, Hakonarson H, Holt PG, Homuth G, Hubner N, Hysi PG, Jarvelin MR, Karlsson R, Koppelman GH, Lau S, Lutz M, Magnusson PKE, Marks GB, Müller-Nurasyid M, Nöthen MM, Paternoster L, Pennell CE, Peters A, Rawlik K, Robertson CF, Rodriguez E, Sebert S, Simpson A, Sleiman PMA, Standl M, Stölzl D, Strauch K, Szwajda A, Tenesa A, Thompson PJ, Ullemar V, Visconti A, Vonk JM, Wang CA, Weidinger S, Wielscher M, Worth CL, Xu CJ, Lee YA. Nat Commun 12 6618 (2021)
  58. Ehrlichia SLiM Ligand Mimetic Activates Notch Signaling in Human Monocytes. Patterson LL, Velayutham TS, Byerly CD, Bui DC, Patel J, Veljkovic V, Paessler S, McBride JW. mBio 13 e0007622 (2022)
  59. Mutational analysis of JAG1 gene in non-syndromic tetralogy of Fallot children. Kola S, Koneti NR, Golla JP, Akka J, Gundimeda SD, Mundluru HP. Clin Chim Acta 412 2232-2236 (2011)
  60. Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1. Schuster-Gossler K, Cordes R, Müller J, Geffers I, Delany-Heiken P, Taft M, Preller M, Gossler A. Genetics 202 1119-1133 (2016)
  61. Combining genetic and biophysical approaches to probe the structure and function relationships of the notch receptor. Baron M. Mol Membr Biol 34 33-49 (2017)
  62. Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis. Zhang H, Shang R, Bi P. PLoS Genet 17 e1009729 (2021)
  63. The multifunctional role of Notch signaling in multiple myeloma. Sabol HM, Delgado-Calle J. J Cancer Metastasis Treat 7 20 (2021)
  64. The tetralogy of Fallot-associated G274D mutation impairs folding of the second epidermal growth factor repeat in Jagged-1. Guarnaccia C, Dhir S, Pintar A, Pongor S. FEBS J 276 6247-6257 (2009)
  65. Affinity-matured DLL4 ligands as broad-spectrum modulators of Notch signaling. Gonzalez-Perez D, Das S, Antfolk D, Ahsan HS, Medina E, Dundes CE, Jokhai RT, Egan ED, Blacklow SC, Loh KM, Rodriguez PC, Luca VC. Nat Chem Biol 19 9-17 (2023)
  66. Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice. Hirano KI, Suganami A, Tamura Y, Yagita H, Habu S, Kitagawa M, Sato T, Hozumi K. Elife 9 e50979 (2020)
  67. Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma. Aoyama K, Ota Y, Kajiwara K, Hirayama N, Kimura M. Biochem Biophys Res Commun 452 980-985 (2014)
  68. Delta-like 1-Lysine613 regulates notch signaling. Zhang L, Widau RC, Herring BP, Gallagher PJ. Biochim Biophys Acta 1813 2036-2043 (2011)
  69. Notch-Jagged signaling complex defined by an interaction mosaic. Zeronian MR, Klykov O, Portell I de Montserrat J, Konijnenberg MJ, Gaur A, Scheltema RA, Janssen BJC. Proc Natl Acad Sci U S A 118 e2102502118 (2021)
  70. Letter Novel and recurrent JAG1 mutations in patients with tetralogy of Fallot. Guida V, Chiappe F, Ferese R, Usala G, Maestrale G, Iannascoli C, Bellacchio E, Mingarelli R, Digilio MC, Marino B, Uda M, De Luca A, Dallapiccola B. Clin Genet 80 591-594 (2011)
  71. The role of Jagged1 as a dynamic switch of cancer cell plasticity in PDAC assembloids. Choi JI, Rim JH, Jang SI, Park JS, Park H, Cho JH, Lim JB. Theranostics 12 4431-4445 (2022)
  72. Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast Cancer. Silva G, Sales-Dias J, Casal D, Alves S, Domenici G, Barreto C, Matos C, Lemos AR, Matias AT, Kucheryava K, Ferreira A, Moita MR, Braga S, Brito C, Cabral MG, Casalou C, Barral DC, Sousa PMF, Videira PA, Bandeiras TM, Barbas A. Cancers (Basel) 13 4074 (2021)
  73. Neurogenin 2 enhances the neuronal differentiation of skin-derived precursors. Dai X, Lu X, Cheng F, Hao H, Qian T, Yu W, Tang L, Li L. Int J Neurosci 125 367-374 (2015)
  74. Exon 6 of human JAG1 encodes a conserved structural unit. Pintar A, Guarnaccia C, Dhir S, Pongor S. BMC Struct Biol 9 43 (2009)
  75. IMP regulates Kuzbanian to control the timing of Notch signalling in Drosophila follicle cells. Fic W, Faria C, St Johnston D. Development 146 dev168963 (2019)
  76. Notch activation is required for downregulation of HoxA3-dependent endothelial cell phenotype during blood formation. Sanghez V, Luzzi A, Clarke D, Kee D, Beuder S, Rux D, Osawa M, Madrenas J, Chou TF, Kyba M, Iacovino M. PLoS One 12 e0186818 (2017)
  77. (1)H, (13)C and (15)N assignments of EGF domains 4 to 7 of human Notch-1. Weisshuhn PC, Handford PA, Redfield C. Biomol NMR Assign 9 275-279 (2015)
  78. (1)H, (13)C and (15)N assignments of EGF domains 8-11 of human Notch-1. Weisshuhn PC, Handford PA, Redfield C. Biomol NMR Assign 9 375-379 (2015)
  79. Identification and characterization of a novel Sso7d scaffold-based binder against Notch1. Gocha T, Rao BM, DasGupta R. Sci Rep 7 12021 (2017)
  80. JAGGED1 gene variations in Chinese twin sisters with Alagille syndrome. Xie X, Lu Y, Wang X, Wu B, Yu H. Int J Clin Exp Pathol 8 8506-8511 (2015)
  81. Molecular modeling and molecular dynamics simulation studies of Delta-Notch complex. Majumder R, Roy S, Thakur A. J Biomol Struct Dyn 29 297-310 (2011)
  82. Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors. Silva G, Rodrigues AF, Ferreira S, Matos C, Eleutério RP, Marques G, Kucheryava K, Lemos AR, Sousa PMF, Castro R, Barbas A, Simão D, Alves PM. Biomolecules 13 459 (2023)
  83. The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling. Martins T, Meng Y, Korona B, Suckling R, Johnson S, Handford PA, Lea SM, Bray SJ. EMBO Rep 22 e52729 (2021)
  84. Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes. Liu LP, Zheng DX, Xu ZF, Zhou HC, Wang YC, Zhou H, Ge JY, Sako D, Li M, Akimoto K, Li YM, Zheng YW. Cells 11 70 (2021)
  85. Analysis of Delta-Notch interaction by molecular modeling and molecular dynamic simulation studies. Majumder R, Roy S, Thakur AR. J Biomol Struct Dyn 30 13-29 (2012)
  86. Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties. Sargis T, Youn SW, Thakkar K, Naiche LA, Paik NY, Pajcini KV, Kitajewski JK. Angiogenesis 26 249-263 (2023)
  87. Statistical platform to discern spatial and temporal coordination of endothelial sprouting. Yuen WW, Du NR, Shvartsman D, Arany PR, Lam H, Mooney DJ. Integr Biol (Camb) 4 292-300 (2012)
  88. Refining a Jagged edge. Blacklow SC. Structure 21 2100-2101 (2013)
  89. Studying the NOTCH Signaling Pathway Activation in Kidney Biopsies. Márquez-Expósito L, Lavoz C, Cantero-Navarro E, Rodrigues-Diez RR, Mezzano S, Ruiz-Ortega M. Methods Mol Biol 2472 187-196 (2022)
  90. Tyrosine-phosphorylated DNER sensitizes insulin signaling in hepatic gluconeogenesis by inducing proteasomal degradation of TRB3. Li J, Huang Y, Yang X, Cai Y, Wang Y, Dai W, Jiang L, Wang C, Wen Z. Mol Metab 83 101927 (2024)


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