DLL1是Delta類的Notch受體配體，可以激活Notch信號通路，參與細胞分化、增殖和凋亡等生物學過程。最近的研究表明，DLL1在腫瘤中的表達水平與腫瘤細胞增殖和轉移相關，因此被認為是腫瘤治療的一個潛在靶點。此外，DLL1也被發現在免疫細胞中具有重要的免疫調節功能，具有治療自身免疫性疾病和腫瘤的潛在應用前景。

Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner. Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD). Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation. Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner. During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries. During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis. Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell. Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B-cells. Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor. Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression. Also plays a role during pancreatic cell development. During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression. Controls sprouting angiogenesis and subsequent vertical branch formation througth regulation on tip cell differentiation. Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. Plays a role during inner ear development; negatively regulates auditory hair cell differentiation. Plays a role during nephron development through Notch signaling pathway. Regulates growth, blood pressure and energy homeostasis.

1. Abnormal DLL1 methylation and expression observed in early gastric lesions and in gastric cancers may be relevant to the pathogenesis of gastric cancer. PMID: 29526075
2. This study suggested that miR-34a-5p, DLL1 and the ATF2/ATF3/ATF4 signaling pathway-associated genes are the potential diagnostic and/or therapeutic targets for an effective chemotherapy of osteosarcoma. PMID: 28281638
3. miR-34a contributes to chondrocyte death, causing Osteoarthritis progression through DLL1 and modulation of the PI3K/AKT pathway. PMID: 30048987
4. Soluble DLL1 was significantly increased in uterine lavage samples of infertile women compared with fertile women in the secretory phase of the menstrual cycle. PMID: 26616664
5. Neuroblastoma cells were transfected with miRNA-34 family members, and the effect of miRNAs transfection on DLL1 mRNA expression levels, on cell differentiation, proliferation and apoptosis was measured PMID: 28525978
6. Highly methylated domains containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in autism spectrum disorders children than in controls. PMID: 28018572
7. The DLK1 inhibited the odontoblastic differentiation of hDPSCs, which maybe through ERK signalling pathway. PMID: 28205268
8. the effects of two Notch ligands, i.e., Jagged1 and DLL1, on murine and human hematopoiesis in vitro. Our observations indicate that the stromal expression of Notch ligands increases the production of both the total and phenotypically early murine and human hematopoietic cells in the co-culture. PMID: 28537242
9. DLL1-mediated Notch signaling is critical for proper bone remodeling as it regulates the differentiation and function of both osteoblasts and osteoclasts. PMID: 27735989
10. Human Jagged-1 induced the proliferation and differentiation of CD133+ cord blood progenitors compared with hDll-1. Thus, hJagged-1 signaling in the bone marrow niche may be used to expand EPCs for therapeutic angiogenesis PMID: 27846321
11. Gain-of-function and loss-of-function studies demonstrated that miR-130b-3p could inhibit breast carcinoma cell invasion and migration by directly targeting the Notch ligand Delta-like 1 (DLL1). PMID: 28163094
12. Mir-34a functions as a regulator by decreasing the expression of NOTCH1 and DLL1. Our study is the first to identify a correlation between mir-34a and its target genes NOTCH1 and DLL1 in endometrial adenocarcinoma PMID: 27039384
13. High DLL1 levels were associate with reduced exercise capacity and diastolic dysfunction in chronic heart failure patients. PMID: 26211721
14. Although Delta1 activates signal transducer and activator of transcription 3 signaling similarly to the gp130-activating cytokine interleukin-6 (IL-6), it has opposite effects on myeloid cell production. PMID: 24243972
15. Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin. PMID: 24714813
16. altered Notch signaling via methylation of DLL1 is likely involved in possible disease-related mechanisms of early onset preeclampsia PMID: 26014475
17. Data suggest that overexpression of Delta-Like1 (DLL1) in small cell lung cancer may increase the sensitivity of cells to chemotherapeutic agents. PMID: 23769341
18. determined the X-ray crystal structure of the extracellular domain of the Notch ligand delta-like ligand-1 (Dll-1) PMID: 25715738
19. Delta-like 1-mediated Notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells. PMID: 25367118
20. Dengue virus up-regulates expression of notch ligands Dll1 and Dll4 through interferon-beta signalling pathway. PMID: 25041739
21. Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. PMID: 24025447
22. direct measurement of the binding affinity of Notch1 EGF repeats 6-15 for Dll1 and Dll4 revealed that Dll4 binds with at least an order of magnitude higher affinity than Dll1 PMID: 23839946
23. Overexpresion of DLL1 in endothelial cells inhibited cell proliferation, but did not affect cell migration, sprouting angiogenesis or cell adhesion. PMID: 23300864
24. MiR-34a reduced cell proliferation and invasiveness, at least, partially through its inhibitory effect on DLL1 in choriocarcinoma. PMID: 23327670
25. with supervised resistance exercise training, expression of Notch1 and Hes6 genes were increased and Delta-like 1 and Numb expression were decreased. PMID: 17301032
26. these results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand. PMID: 20170633
27. we have investigated their influence on early human hematopoiesis and show that Jagged2 affects hematopoietic lineage decisions very similarly as Delta-like-1 and -4, but very different from Jagged1 PMID: 21372153
28. DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 Visceral leishmaniasis susceptibility gene. PMID: 21742847
29. Notch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas. PMID: 22080880
30. regulates Notch1 signaling through disruption of the Notch1-IC-RBP-Jk transcription activator complex PMID: 21643850
31. Twenty-one SNPs were genotyped in 941 visceral leishmaniasis cases and 992 controls. Gene expression profiling was done and DLL1 was the only gene to show differential expression that was higher (P<0.0001) in pre- compared to post-treatment samples. PMID: 22561395
32. Relapse-free survival and overall survival showed a significantly shorter survival in acute myeloid leukemia patients with higher Notch1 expression, higher Jagged1 expression, or higher Delta1 expression. PMID: 20812035
33. Dll1 and Notch interaction accelerates multiple myeloma disease development by promoting CD138+ MM-cell proliferation. PMID: 22094583
34. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma PMID: 21931765
35. as compared to MSC, OP9 cells were more efficient at inducing self-renewal and/or de novo generation of primitive (CD34(+) CD38(-) Lin(-)) cells, and suggest that such effects were due, at least in part, to the presence of Jagged-1 and DL1. PMID: 21911304
36. An anti-delta1 Notch protein-blocking monoclonal antibody is able to prolong allograft survival in a fully histocompatibility-mismatched model of cardiac transplantation. PMID: 21949024
37. growth rate of Delta1-deficient dental pulp stem cells was significantly suppressed as compared with wild type cells PMID: 21392732
38. 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 late placenta PMID: 21726900
39. The stromal cell-mediated antiapoptotic effect on B- ALL cells is mediated by Notch-3 and -4 or Jagged-1/-2 and DLL-1 in a synergistic manner. PMID: 21602525
40. Notch1 and its ligand Delta-like 1(DLL1) are miR-449 bona fide targets PMID: 21602795
41. findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in Holoprosencephaly. PMID: 21196490
42. In this study, Delta 1 ligand was detected in the lining epithelium of human periapical cysts with limited inflammation, showing Notch pathway activation in those cells. PMID: 21238798
43. Delta1 protein is involved in the cytodifferentiation of squamous odontogenic tumors of the mandible. PMID: 20554499
44. revealed a striking difference between the responses of Notch to trans- and cis-Delta: whereas the response to trans-Delta is graded, the response to cis-Delta is sharp and occurs at a fixed threshold, independent of trans-Delta PMID: 20418862
45. DLL1 was found downregulated in immune thrombocytopenic purpura. PMID: 19603167
46. Delta-1 can enhance myeloid and lymphoid marrow-repopulating ability and promote the generation of thymus-repopulating T cell precursors. PMID: 12393852
47. suppresses the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines PMID: 12684674
48. Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus PMID: 12794186
49. Delta and Jagged undergo ADAM-mediated ectodomain processing followed by PS-mediated intramembrane proteolysis to release signaling fragments PMID: 12826675
50. induces a NIH 3T3 cell tranformed phenotype mediated by FGF signaling. PMID: 14769803

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Apical cell membrane; Single-pass type I membrane protein. Cell junction, adherens junction. Membrane raft.

Expressed in heart and pancreas, with lower expression in brain and muscle and almost no expression in placenta, lung, liver and kidney.

HGNC: 2908

OMIM: 606582

KEGG: hsa:28514

STRING: 9606.ENSP00000355718

UniGene: Hs.379912