Notch protein

Fig. 12.2. Model of Notch signalling. The Notch protein is a ligand activated transmembrane receptor which is subject to proteolysis of the intracellular domain upon ligand binding. The nature of the protease involved is still a matter of debate. The proteolytically released intranceUu-lar domain of Notch (NICD) translocates into the nucleus where it interacts with a family of transcription factors, the CSL proteins, resulting in a change in transcription of target genes.

Secretase amyloid precursor protein and Notch protein. Gamma(y)-secretase is com-... 

Avagacestat (BMS-708163) is a GSI developed for selective inhibition of APP over Notch cleavage. Avagacestat inhibition of APP and Notch cleavage was evaluated in cell culture by measuring levels of Ap and human Notch proteins. Avagacestat reduces CSF Ap levels without causing Notch-related toxicities [413],... 

NOTCH proteins participate in conserved pathways that regulate cellular differentiation, proliferation, and cell death. Mammalian NOTCH receptors are single-pass transmembrane proteins that transmit juxtacrine signals initiated by ligands of the Delta, Serrate, or Lag-2 family [122, 123], When ligands bind to the extracellular domain of NOTCH1, sequential proteolytic processing events lead to the... 

Neu protein, which takes part in embryonic differentiation and Notch protein, a receptor protein in the plasma membrane that functions in developmentally important signaling (Chapter 14). Besides the EGF domain, these proteins contain domains found in other proteins. For example, TPA possesses a trypsin domain, a common feature in enzymes that degrade proteins. 

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