γ-Secretase Mediated Proteolysis: At the Cutting Edge of Notch Signaling

摘要: Notch proteins are evolutionary conserved transmembrane receptors used by metazoans to direct cell fate decisions, proliferation, differentiation and death at all stages of development, including self-renewing adult tissues. signaling is a well-established example pathway that mediated Regulated Intramembrane Proteolysis (RIP). Upon binding ligand, the receptor undergoes successive proteolytic cleavages – an ectodomain shedding cleavage followed intramembrane proteolysis γ-secretase. This process releases intracellular domain, which translocates nucleus activate its target genes. Deciphering mechanism for activation relied on convergence previously independent fields research, revealing resembled another Type I membrane protein, amyloid-γ precursor in both proteolytically cleaved within their domains (TMDs) same protease, γ-secretase, whose catalytic center resided protein Presenilin. has continued emerge as exciting research area biology. Recent studies γ-secretase function have begun reveal molecular details involved events well importance endocytosis endosomal sorting key regulators