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Gene Review

DLL1  -  delta-like 1 (Drosophila)

Homo sapiens

Synonyms: DELTA1, DL1, Delta, Delta-like protein 1, Delta1, ...
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Disease relevance of DLL1


Psychiatry related information on DLL1

  • Comparisons with structural data allow us to rationalize individual differences between Delta Ho(obs) (and Delta So(obs)) for the four complexes [6].
  • We recently reported that pilocarpine, an orally active muscarinic agonist, induced REM sleep and reduced Stage 3 & 4 (Delta) sleep in young normal volunteers [7].
  • RESULTS: Five children with DM (33%) had profound nocturnal hypoglycemia, which was associated with increased sleep efficiency, increased slow wave sleep, and increased Delta power in spectral analysis of the electroencephalogram [8].
  • PASIs and Delta PASIs were recalculated based on the new models and all scoring systems were validated by analysing their relationship to patients' self-assessments [9].
  • Patterns of antischistosomal drug usage in Qalyubia Governorate of the Nile Delta [10].

High impact information on DLL1

  • This approach depends on accurate estimates of the carbon isotopic discrimination of terrestrial photosynthesis (Delta; ref. 5) at large regional scales, yet terrestrial ecosystem heterogeneity makes such estimates problematic [11].
  • Our estimates indicate a large (5 6 per thousand) seasonal variation in Delta of the temperate North American biosphere, with maximum discrimination occurring in late spring, coincident with the onset of production [11].
  • Here we report the isolation of an HTLV-III-related retrovirus, STLV-III/Delta, from rhesus macaques (Macaca mulatta) with transmissible simian AIDS (SAIDS) and from asymptomatic sooty mangabeys (Cercocebus atys) [12].
  • This enhancer activates transcription from the V delta 1 and V delta 3 promoters as well as from heterologous promoters [13].
  • For example, endocytosis of Delta, the ligand of Notch, is needed for activation of the signal [14].

Chemical compound and disease context of DLL1

  • DESIGN AND METHODS: HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay [15].
  • Fluorescence-activated cell sorter analysis, fluorescence microscopy, and measures of mitochondrial membrane potential (Delta Psi m) demonstrated that arsenic trioxide alone was sufficient to induce programmed cell death in all HTLV-1 and -2 cells tested and in ATLL patient samples [16].
  • These results suggest that elevated glucose produces early initiator caspase activation, followed by Delta Psi(M) changes, in neuroblastoma cells; in turn, IGF-I prevents apoptosis by preventing downstream caspase activation, maintaining Delta Psi(M) and regulating Bcl proteins [17].
  • Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively [18].
  • HHV-8 gB Delta TM, but not gB Delta TM-RGA, induced FAK phosphorylation in target cells, which was in part dependent on the presence of alpha 3 beta 1 integrin [19].

Biological context of DLL1


Anatomical context of DLL1


Associations of DLL1 with chemical compounds

  • We identified the lysine residue targeted by the monoubiquitination event and confirmed its importance for activation of Notch receptor by its ligand, Delta-like 1 [29].
  • Furthermore, we identified serine/threonine kinase activity associated with p60CD delta 1 that required either Mn2+ or Mg2+ for optimal activity [5].
  • The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease [30].
  • The Notch ligand, Delta-1, alters retinoic acid (RA)-induced neutrophilic differentiation into monocytic and reduces RA-induced apoptosis in NB4 cells [31].
  • Furthermore, ROS scavengers, such as glutathione (GSH) and catalase, maintained Delta psi(m) and prevented apoptosis upon treatment [32].

Physical interactions of DLL1

  • Delta-1 stimulation did not increase the binding of annexin V, a marker for apoptotic cells in either cell line [3].
  • We identify by in silico screening a number of additional candidate target genes, which are recognized by Mash1 and Brn proteins through a DNA-binding motif similar to that found in the Delta1 gene and present a broad range of activities [33].

Regulatory relationships of DLL1

  • TNF stimulation of MCF-7 and foreskin fibroblasts for 5-15 min induced approximately 50 and 240% increases in phosphorylation of p60CD delta 1, respectively [5].
  • Our findings also suggest a mechanism for the establishment of the cell selection process, lateral inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells switches to single Delta1-presenting neurons as FGF activity declines in the newly formed neuroepithelium [34].
  • GM-CSF-induced growth suppression and apoptosis of U937 cells were partially rescued by incubation with Delta-1 [35].
  • In addition, we have found that some gamma delta T cell clones bearing the V delta 1 segment were activated by direct mAb engagement of ICAM-3 in the absence of TcR/CD3 occupancy [36].
  • The outgrowth of simian gamma delta T cells in response to Daudi cells is similar to that in humans, but the exposure to IL-2 stimulates preferentially the simian V delta 1 subset rather than the V gamma 9/V delta 2 subset as found in humans [37].

Other interactions of DLL1


Analytical, diagnostic and therapeutic context of DLL1

  • We detected that the mRNA of Notch ligands such as Jagged1, Delta1 and Delta4 could express in hYSECs after contacted culture with UCB-CD34(+) cells but not the noncontacted cells by RT-PCR analysis [40].
  • Intravenous transplantation of treated cultures into immune-deficient mice revealed that h Delta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo [41].
  • Limiting-dilution and clonal analysis, fetal thymic organ cultures, and culture onto Notch ligand Delta-like-1-expressing OP9 cells, showed that although CD34(+)CD45RA(hi)CD7(+) HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages [42].
  • Using a novel culture system with complexed, soluble Notch ligands that allows the titration of T cell lineage commitment, we find that these precursors are highly sensitive to both Delta and Jagged ligands [43].
  • Immobilization of Notch ligand, Delta-1, is required for induction of notch signaling [44].


  1. The Notch pathway in ovarian carcinomas and adenomas. Hopfer, O., Zwahlen, D., Fey, M.F., Aebi, S. Br. J. Cancer (2005) [Pubmed]
  2. A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein. Tohda, S., Sakano, S., Ohsawa, M., Murakami, N., Nara, N. Br. J. Haematol. (2002) [Pubmed]
  3. Cellular analysis of growth suppression induced by the Notch ligands, Delta-1 and Jagged-1 in two myeloid leukemia cell lines. Murata-Ohsawa, M., Tohda, S., Nara, N. Int. J. Mol. Med. (2004) [Pubmed]
  4. Delta-1 negatively regulates the transition from prehypertrophic to hypertrophic chondrocytes during cartilage formation. Crowe, R., Zikherman, J., Niswander, L. Development (1999) [Pubmed]
  5. Identification of a protein kinase associated with the cytoplasmic domain of the p60 tumor necrosis factor receptor. Darnay, B.G., Reddy, S.A., Aggarwal, B.B. J. Biol. Chem. (1994) [Pubmed]
  6. Sequence-specific DNA-binding dominated by dehydration. Lundbäck, T., Härd, T. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. The cholinergic REM sleep induction test with pilocarpine in mildly depressed patients and normal controls. Lauriello, J., Kenny, W.M., Sutton, L., Golshan, S., Ruiz, C., Kelsoe, J., Rapaport, M., Gillin, J.C. Biol. Psychiatry (1993) [Pubmed]
  8. Interactions between hypoglycemia and sleep architecture in children with type 1 diabetes mellitus. Pillar, G., Schuscheim, G., Weiss, R., Malhotra, A., McCowen, K.C., Shlitner, A., Peled, N., Shehadeh, N. J. Pediatr. (2003) [Pubmed]
  9. Rethinking the Psoriasis Area and Severity Index: the impact of area should be increased. Jacobson, C.C., Kimball, A.B. Br. J. Dermatol. (2004) [Pubmed]
  10. Patterns of antischistosomal drug usage in Qalyubia Governorate of the Nile Delta. McNeeley, D.F., Habib, M.A., El Alamy, M.A., Cline, B.L. Am. J. Trop. Med. Hyg. (1982) [Pubmed]
  11. Plant biomarkers in aerosols record isotopic discrimination of terrestrial photosynthesis. Conte, M.H., Weber, J.C. Nature (2002) [Pubmed]
  12. Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Murphey-Corb, M., Martin, L.N., Rangan, S.R., Baskin, G.B., Gormus, B.J., Wolf, R.H., Andes, W.A., West, M., Montelaro, R.C. Nature (1986) [Pubmed]
  13. A T cell-specific transcriptional enhancer within the human T cell receptor delta locus. Redondo, J.M., Hata, S., Brocklehurst, C., Krangel, M.S. Science (1990) [Pubmed]
  14. Modulation of developmental signals by endocytosis: different means and many ends. Piddini, E., Vincent, J.P. Curr. Opin. Cell Biol. (2003) [Pubmed]
  15. Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study. Masquelier, B., Descamps, D., Carrière, I., Ferchal, F., Collin, G., Denayrolles, M., Ruffault, A., Chanzy, B., Izopet, J., Buffet-Janvresse, C., Schmitt, M.P., Race, E., Fleury, H.J., Aboulker, J.P., Yeni, P., Brun-Vézinet, F. Antivir. Ther. (Lond.) (1999) [Pubmed]
  16. Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1- and type 2-infected cells by a caspase-3-dependent mechanism involving Bcl-2 cleavage. Mahieux, R., Pise-Masison, C., Gessain, A., Brady, J.N., Olivier, R., Perret, E., Misteli, T., Nicot, C. Blood (2001) [Pubmed]
  17. Insulin-like growth factor-I regulates glucose-induced mitochondrial depolarization and apoptosis in human neuroblastoma. Leinninger, G.M., Russell, J.W., van Golen, C.M., Berent, A., Feldman, E.L. Cell Death Differ. (2004) [Pubmed]
  18. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy. Ruggenenti, P., Perna, A., Remuzzi, G. J. Am. Soc. Nephrol. (2001) [Pubmed]
  19. Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 envelope glycoprotein gB induces the integrin-dependent focal adhesion kinase-Src-phosphatidylinositol 3-kinase-rho GTPase signal pathways and cytoskeletal rearrangements. Sharma-Walia, N., Naranatt, P.P., Krishnan, H.H., Zeng, L., Chandran, B. J. Virol. (2004) [Pubmed]
  20. Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Jarriault, S., Le Bail, O., Hirsinger, E., Pourquié, O., Logeat, F., Strong, C.F., Brou, C., Seidah, N.G., Isra l, A. Mol. Cell. Biol. (1998) [Pubmed]
  21. Extrathymic generation of tumor-specific T cells from genetically engineered human hematopoietic stem cells via Notch signaling. Zhao, Y., Parkhurst, M.R., Zheng, Z., Cohen, C.J., Riley, J.P., Gattinoni, L., Restifo, N.P., Rosenberg, S.A., Morgan, R.A. Cancer Res. (2007) [Pubmed]
  22. Altered Notch ligand expression in human liver disease: further evidence for a role of the Notch signaling pathway in hepatic neovascularization and biliary ductular defects. Nijjar, S.S., Wallace, L., Crosby, H.A., Hubscher, S.G., Strain, A.J. Am. J. Pathol. (2002) [Pubmed]
  23. The Notch signaling pathway is related to neurovascular progression of pancreatic cancer. Büchler, P., Gazdhar, A., Schubert, M., Giese, N., Reber, H.A., Hines, O.J., Giese, T., Ceyhan, G.O., Müller, M., Büchler, M.W., Friess, H. Ann. Surg. (2005) [Pubmed]
  24. Effects of Delta1 and Jagged1 on early human hematopoiesis: correlation with expression of notch signaling-related genes in CD34+ cells. Neves, H., Weerkamp, F., Gomes, A.C., Naber, B.A., Gameiro, P., Becker, J.D., Lúcio, P., Clode, N., van Dongen, J.J., Staal, F.J., Parreira, L. Stem Cells (2006) [Pubmed]
  25. Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines. Tohda, S., Murata-Ohsawa, M., Sakano, S., Nara, N. Int. J. Oncol. (2003) [Pubmed]
  26. Distribution of presenilin 1 and 2 and their relation to Notch receptors and ligands in human embryonic/foetal central nervous system. Kostyszyn, B., Cowburn, R.F., Seiger, A., Kjaeldgaard, A., Sundström, E. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  27. Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. Jaleco, A.C., Neves, H., Hooijberg, E., Gameiro, P., Clode, N., Haury, M., Henrique, D., Parreira, L. J. Exp. Med. (2001) [Pubmed]
  28. Monocytes express high amounts of Notch and undergo cytokine specific apoptosis following interaction with the Notch ligand, Delta-1. Ohishi, K., Varnum-Finney, B., Flowers, D., Anasetti, C., Myerson, D., Bernstein, I.D. Blood (2000) [Pubmed]
  29. Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor. Gupta-Rossi, N., Six, E., LeBail, O., Logeat, F., Chastagner, P., Olry, A., Israël, A., Brou, C. J. Cell Biol. (2004) [Pubmed]
  30. Tumour necrosis factor (TNF) gene polymorphism in Crohn's disease (CD): influence on disease behaviour? Louis, E., Peeters, M., Franchimont, D., Seidel, L., Fontaine, F., Demolin, G., Croes, F., Dupont, P., Davin, L., Omri, S., Rutgeerts, P., Belaiche, J. Clin. Exp. Immunol. (2000) [Pubmed]
  31. The Notch ligand, Delta-1, alters retinoic acid (RA)-induced neutrophilic differentiation into monocytic and reduces RA-induced apoptosis in NB4 cells. Murata-Ohsawa, M., Tohda, S., Kogoshi, H., Sakano, S., Nara, N. Leuk. Res. (2005) [Pubmed]
  32. Ornithine decarboxylase prevents tumor necrosis factor alpha-induced apoptosis by decreasing intracellular reactive oxygen species. Liu, G.Y., Hung, Y.C., Hsu, P.C., Liao, Y.F., Chang, W.H., Tsay, G.J., Hung, H.C. Apoptosis (2005) [Pubmed]
  33. Proneural bHLH and Brn Proteins Coregulate a Neurogenic Program through Cooperative Binding to a Conserved DNA Motif. Castro, D.S., Skowronska-Krawczyk, D., Armant, O., Donaldson, I.J., Parras, C., Hunt, C., Critchley, J.A., Nguyen, L., Gossler, A., G??ttgens, B., Matter, J.M., Guillemot, F. Dev. Cell (2006) [Pubmed]
  34. FGF-dependent Notch signaling maintains the spinal cord stem zone. Akai, J., Halley, P.A., Storey, K.G. Genes Dev. (2005) [Pubmed]
  35. The Notch ligand, Delta-1, partially inhibits GM-CSF-induced differentiation and apoptosis along with reducing the cleavage of PARP in U937 cells. Murata-Ohsawa, M., Tohda, S., Sakano, S., Nara, N. Int. J. Mol. Med. (2004) [Pubmed]
  36. ICAM-3, the third LFA-1 counterreceptor, is a co-stimulatory molecule for both resting and activated T lymphocytes. Hernandez-Caselles, T., Rubio, G., Campanero, M.R., del Pozo, M.A., Muro, M., Sanchez-Madrid, F., Aparicio, P. Eur. J. Immunol. (1993) [Pubmed]
  37. Gamma delta T cells in rhesus monkeys and their response to simian immunodeficiency virus (SIV) infection. Gan, Y.H., Pauza, C.D., Malkovsky, M. Clin. Exp. Immunol. (1995) [Pubmed]
  38. Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation. Shimizu, K., Chiba, S., Saito, T., Kumano, K., Takahashi, T., Hirai, H. J. Biol. Chem. (2001) [Pubmed]
  39. The Notch ligand, Delta-1, reduces TNF-alpha-induced growth suppression and apoptosis by decreasing activation of caspases in U937 cells. Murata-Ohsawa, M., Tohda, S., Kogoshi, H., Nara, N. Int. J. Mol. Med. (2004) [Pubmed]
  40. Effects of human yolk sac endothelial cells on supporting expansion of hematopoietic stem/progenitor cells from cord blood. Hu, L., Cheng, L., Wang, J., Zhao, H., Duan, H., Lu, G. Cell Biol. Int. (2006) [Pubmed]
  41. Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells. Karanu, F.N., Murdoch, B., Miyabayashi, T., Ohno, M., Koremoto, M., Gallacher, L., Wu, D., Itoh, A., Sakano, S., Bhatia, M. Blood (2001) [Pubmed]
  42. Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood. Haddad, R., Guardiola, P., Izac, B., Thibault, C., Radich, J., Delezoide, A.L., Baillou, C., Lemoine, F.M., Gluckman, J.C., Pflumio, F., Canque, B. Blood (2004) [Pubmed]
  43. Bone marrow-derived hemopoietic precursors commit to the T cell lineage only after arrival in the thymic microenvironment. Heinzel, K., Benz, C., Martins, V.C., Haidl, I.D., Bleul, C.C. J. Immunol. (2007) [Pubmed]
  44. Immobilization of Notch ligand, Delta-1, is required for induction of notch signaling. Varnum-Finney, B., Wu, L., Yu, M., Brashem-Stein, C., Staats, S., Flowers, D., Griffin, J.D., Bernstein, I.D. J. Cell. Sci. (2000) [Pubmed]
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