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Notch at a glance

Notch 1 is an evolutionarily conserved 270-300 kDa transmembrane protein with multiple extracellular growth factor-like repeats, and with an intracellular domain consisting of multiple different domain types. It serves as a receptor for membrane ligands such as DLL1, Jagged 1 (CD339), and Jagged 2, and regulates cell fate decisions. Upon ligand binding the transmembrane form of Notch 1 is repeatedly cleaved to provide approximately 120 kDa Notch intracellular fragment (NICD), which translocates into the nucleus and acts as a part of transcriptional complexes that alter differentiation, proliferation, and apoptosis. The highest level of Notch 1 expression is in bone marrow progenitor cells, brain, lung and thymus. Similarly to Notch 1, its paralogs Notch 2-4 interact with various members of DLL and Jagged group of ligands. Notch ligands activate Notch signaling pathway, except DLL3, which seems to act as an antagonist.

Notch signaling plays important roles in both developing and mature immune cells. It affects both innate and adaptive immunity. Notch is essential for T cell lineage commitment from the common lymphoid progenitor and later it is important also for Th commitment and differentiation, as well as for some other immune cells fate. Interactions between Notch receptors on particular T cells, its ligands on antigen presenting cells, together with effect of various cytokines forms a complex immune signaling network , where fine tuning and crosstalk takes part. In mice, moreover, Notch expression was demonstrated also on bone marrow-derived mast cells and peritoneal mast cells.

Due to the importance of Notch system for proper development and function of the immune system, its dysregulation has multiple effects, including affected hematopoiesis and cell differentiation, autoimmune diseases, leukemia, tumor-induced immunosuppression and other. Hence it is also not so simple to choose optimal intervention, as Notch controls various T cell types, including those with opposing functions, as well as dendritic cells, macrophages, and myeloid-derived suppressor cells. Notch plays crucial roles in initiation, progression and relapse of various cancers, but on the other hand, it is also important for anti-cancer immunity functions. Therapies thus must be well targeted with respect to the particular conditions.

Fig. 1: Schematic drawing of Notch signaling. After binding to its ligands, Notch is being cleaved by extracellular metalloprotease CD156 and subsequently by intracellular gamma-secretase to provide Notch intracellular fragment, which takes part in downstream signaling.

The mouse monoclonal antibody mN1A recognizes an intracellular epitope of human and murine Notch1, mainly its activated form, and can be used for flow cytometry, Western blotting, immunocytochemistry, immunohistochemistry and immunoprecipitation.

Formats:
Purified (11-651-C100)
PE (1P-651-C100)
APC (1A-651-C100).

Fig. 2: Flow cytometry intracellular staining patterns of PHA stimulated human peripheral whole blood stained using anti-Notch1 (mN1A) PE antibody (3 μg/ml, left) or mouse IgG1 isotype control (MOPC-21) PE antibody (3 μg/ml, right).

Further reading:

Tu LL et al.: Notch signaling is an important regulator of type 2 immunity. JEM 2005 (202/8) 1037-1042.

Nakano N et al.: Notch signaling confers antigen-presenting cell functions on mast cells. J Allergy Clin Immunol. 2009 (123) 74-81.

Janghorban M et al.: Notch signaling as a regulator of the tumor immune response: To target or not to target? Front Immunol. 2018 (9) 01649.

Brandstadter JD and Maillard I: Notch signaling in T cell homeostasis and differentiation. Open Biol. 2019 (9) 190187.

Li X et al.: The Notch signaling pathway: A potential target for cancer immunotherapy. J Hematol Oncol. 2023 (16) 45.