Advances in Non-Canonical Notch Signaling Pathway
CHEN Yangyu, LÜ Zhiyi*
The Notch signaling pathway is an evolutionarily highly conserved intercellular signal transduction pathway, and its dysfunction is closely associated with various diseases such as congenital heart disease,leukemia and Alzheimer’s disease. In addition to the canonical linear regulatory axis of “ligand-receptor-transcription factor”, recent studies have identified a variety of non-canonical activation modes, which have greatly expanded the regulatory network of Notch signaling and enriched the understanding of its functional diversity. Thispaper systematically summarizes the classification, molecular mechanisms and pathophysiological significance offour types of non-canonical Notch signal transduction pathways. These non-canonical pathways are characterizedby rapid stress responsiveness, signal network integration and subcellular localization specificity, and play keyroles in developmental homeostasis, immune regulation and tumorigenesis. An in-depth dissection of these noncanonical signaling networks not only provides a new perspective for elucidating the complex regulatory mechanisms of the Notch pathway, but also opens up new directions for targeted therapies against tumors and cardiovascular diseases.
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