Engineering synthetic agonists for targeted activation of Notch signaling

Sprinzak, D. & Blacklow, S. C. Biophysics of Notch signaling. Annu. Rev. Biophys. 50, 157–189 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou, B. et al. Notch signaling pathway: architecture, disease, and therapeutics. Signal. Transduct. Target. Ther. 7, 1–33 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Garg, V. et al. Mutations in NOTCH1 cause aortic valve disease. Nature 437, 270–274 (2005).

Article  CAS  PubMed  Google Scholar 

Li, L. et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat. Genet. 16, 243–251 (1997).

Article  CAS  PubMed  Google Scholar 

Joutel, A. et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383, 707–710 (1996).

Article  CAS  PubMed  Google Scholar 

Bulman, M. P. et al. Mutations in the human Delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat. Genet. 24, 438–441 (2000).

Article  CAS  PubMed  Google Scholar 

Radtke, F. & Raj, K. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat. Rev. Cancer 3, 756–767 (2003).

Article  CAS  PubMed  Google Scholar 

Hori, K., Sen, A. & Artavanis-Tsakonas, S. Notch signaling at a glance. J. Cell Sci. 126, 2135–2140 (2013).

CAS  PubMed  PubMed Central  Google Scholar 

Andersson, E. R. & Lendahl, U. Therapeutic modulation of Notch signalling—are we there yet? Nat. Rev. Drug Discov. 13, 357–378 (2014).

Article  CAS  PubMed  Google Scholar 

Brandstadter, J. D. & Maillard, I. Notch signalling in T cell homeostasis and differentiation. Open Biol. 9, 190187 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schmitt, T. M. & Zúñiga-Pflücker, J. C. Induction of T cell development from hematopoietic progenitor cells by Delta-like-1 in vitro. Immunity 17, 749–756 (2002).

Article  CAS  PubMed  Google Scholar 

Kelliher, M. A. & Roderick, J. E. NOTCH signaling in T-cell-mediated anti-tumor immunity and T-cell-based immunotherapies. Front. Immunol. 9, 1718 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sierra, R. A. et al. Rescue of Notch-1 signaling in antigen-specific CD8+ T cells overcomes tumor-induced T-cell suppression and enhances immunotherapy in cancer. Cancer Immunol. Res 2, 800–811 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilkens, A. B. et al. Notch1 signaling during CD4+ T-cell activation alters transcription factor networks and enhances antigen responsiveness. Blood 140, 2261–2275 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kondo, T. et al. Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy. Nat. Commun. 8, 15338 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meloty-Kapella, L., Shergill, B., Kuon, J., Botvinick, E. & Weinmaster, G. Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin. Dev. Cell 22, 1299–1312 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, X. & Ha, T. Defining single molecular forces required to activate Integrin and Notch signaling. Science 340, 991–994 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gordon, W. R. et al. Mechanical allostery: evidence for a force requirement in the proteolytic activation of Notch. Dev. Cell 33, 729–736 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rebay, I. et al. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67, 687–699 (1991).

Article  CAS  PubMed  Google Scholar 

Luca, V. C. et al.Structural basis for Notch1 engagement of Delta-like 4. Science 347, 847–853 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luca, V. C. et al. Notch–Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science 355, 1320–1324 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gordon, W. R. et al. Structural basis for autoinhibition of Notch. Nat. Struct. Mol. Biol. 14, 295–300 (2007).

Article  CAS  PubMed  Google Scholar 

De Strooper, B. et al. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518–522 (1999).

Article  PubMed  Google Scholar 

Brou, C. et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol. Cell 5, 207–216 (2000).

Article  CAS  PubMed  Google Scholar 

Schroeter, E. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382–386 (1998).

Article  CAS  PubMed  Google Scholar 

Varnum-Finney, B. et al. Immobilization of Notch ligand, Delta-1, is required for induction of notch signaling. J. Cell Sci. 113, 4313–4318 (2000).

Article  CAS  PubMed  Google Scholar 

Trotman-Grant, A. C. et al. DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system. Nat. Commun. 12, 5023 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, K. et al. Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of Notch3. J. Biol. Chem. 283, 8046–8054 (2008).

Article  CAS  PubMed  Google Scholar 

Tiyanont, K., Wales, T. E., Siebel, C. W., Engen, J. R. & Blacklow, S. C. Insights into Notch3 activation and inhibition mediated by antibodies directed against its negative regulatory region. J. Mol. Biol. 425, 3192–3204 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu, X. et al. Insights into autoregulation of Notch3 from structural and functional studies of its negative regulatory region. Structure 23, 1227–1235 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ilagan, M. X. G., Lim, S., Fulbright, M., Piwnica-Worms, D. & Kopan, R. Real-time imaging of Notch activation with a luciferase complementation-based reporter. Sci. Signal. 4, rs7(2011).

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