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Fig. 2 | BMC Genomics

Fig. 2

From: Twinkle twinkle brittle star: the draft genome of Ophioderma brevispinum (Echinodermata: Ophiuroidea) as a resource for regeneration research

Fig. 2

Simplified diagram of the Notch signaling pathway. The pathway is mediated by juxtacrine signaling that requires direct physical contact between the signaling and receptor cells. The Delta/Serrate (Jagged) ligands and Notch receptors are transmembrane proteins embedded into the plasma membrane of the signaling and receptor cells, respectively. Ligand-receptor interaction triggers conformational changes in the Notch protein that allows for proteolytic cleavage of the receptor by the ADAM metalloprotease and the multiprotein γ-secretase complex. The latter includes the catalytic component presenilin, as well as regulatory/stabilizing subunits nicastrin, Aph-1, and Pen (presenilin enhancer)-2. This proteolytic cleavage releases the Notch intercellular domain that translocates into the nucleus and activates the transcription factor RBP-J by inducing the release of co-repressors (e.g., NCOR, CIR, MINT, and HDAC) and recruitment of co-activators, such as Mastermind (MAM), p300, and NACK. The activated transcription factor complex initiates transcription of the direct targets of the pathway, including Hes and Hey. Even though the pathway itself is conceptually simple, it is subjected to a multitude of regulatory inputs at multiple levels, including receptor post-translational maturation and stability/availability of the key pathway components in both the signaling and receptor cells. One of the properties of the Notch pathway is the ability to sustain itself through a series of feed-forward loops, thus resulting in an all-or-nothing response. For example, NACK, which is a transcriptional co-activator in the pathway is itself positively regulated by Notch. The genes shown in the diagram were searched for and identified in the O. brevispinum draft genome (see Table 5). Three different searches for Notch related genes in the draft genome were performed, designated by green boxes (BLAST, Exonerate, and conserved domain search respectively), filled boxes indicate positive identification

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