Mechanism of action Notch signaling pathway

the notch protein spans cell membrane, part of inside , part outside. ligand proteins binding extracellular domain induce proteolytic cleavage , release of intracellular domain, enters cell nucleus modify gene expression.

the cleavage model first proposed in 1993 based on work done drosophila notch , c. elegans lin-12, informed first oncogenic mutation affecting human notch gene. compelling evidence model provided in 1998 in vivo analysis in drosophila gary struhl , in cell culture raphael kopan. although model disputed, evidence in favor of model irrefutable 2001.

the receptor triggered via direct cell-to-cell contact, in transmembrane proteins of cells in direct contact form ligands bind notch receptor. notch binding allows groups of cells organize such that, if 1 cell expresses given trait, may switched off in neighbouring cells intercellular notch signal. in way, groups of cells influence 1 make large structures. thus, lateral inhibition mechanisms key notch signaling. lin-12 , notch mediate binary cell fate decisions, , lateral inhibition involves feedback mechanisms amplify initial differences.

the notch cascade consists of notch , notch ligands, intracellular proteins transmitting notch signal cell s nucleus. notch/lin-12/glp-1 receptor family found involved in specification of cell fates during development in drosophila , c. elegans.

the intracellular domain of notch forms complex cbf1 , mastermind activate transcription of target genes. structure of complex has been determined.