Notch signaling pathway
The Notch signaling pathway is a highly conserved cell-cell communication mechanism that plays a crucial role in cell fate determination, tissue development, angiogenesis, neural development, and tumorigenesis, among other biological processes.
Notch Receptors: Notch is a single transmembrane protein receptor found in various cell types, waiting for ligand binding on the cell membrane.
Ligands: The ligands for Notch receptors include Delta, Jagged, Serrate, etc., which are also membrane proteins typically expressed on the surface of neighboring cells.
Receptor-Ligand Binding: When the Notch receptor binds to its ligand on an adjacent cell, a series of proteolytic cleavage events are triggered.
Notch Receptor Cleavage: Initially, the extracellular domain of the Notch receptor is cleaved by ADAM proteases after ligand binding, followed by further cleavage of the intracellular domain by the γ-secretase complex.
Nuclear Translocation of Notch Fragment: The cleaved intracellular fragment of Notch (NICD) is released and translocates to the nucleus.
Transcriptional Activation: In the nucleus, NICD binds to the transcription factor RBPJ (CBF1) and recruits other transcriptional co-activators to activate target genes of the Notch signaling pathway.
Target Gene Expression: The activation of these target genes is involved in regulating processes such as cell proliferation, differentiation, and apoptosis.
Signal Termination: The activity of the Notch signal is finely regulated by various mechanisms, including proteolytic cleavage, negative feedback regulation, and protein degradation.
Biological Functions: The Notch signaling pathway is involved in regulating embryonic development, tissue regeneration, cell fate determination, cell cycle control, and apoptosis.
Disease Association: Abnormal activation or inhibition of the Notch signaling pathway is associated with various diseases, including certain types of cancer, cardiovascular diseases, and neurodegenerative diseases.
Therapeutic Potential: The regulatory mechanisms of the Notch signaling pathway provide new strategies for treating related diseases, including the development of small molecule drugs targeting Notch receptors or ligands.
Drug Targets
