Gamma-secretase and the intramembrane proteolysis of Notch.
Gamma-secretase is the crucial proteolytic activity that releases the Notch intracellular domain and is therefore a central player in the canonical Notch-signaling transduction pathway. We discuss here briefly the discovery of gamma-secretase and what is known on its structure and function. Recent work also indicates that the assembly and activity of gamma-secretase might be regulated by novel cell biological mechanisms. Finally we explore the recent insight that there are several gamma-secretase complexes in mammalian and discuss possibilities to use gamma-secretase as a drug target in Alzheimer's disease and cancer.
Jorissen
Ellen
E
Center for Human Genetics, KULeuven, Leuven, Belgium.
De Strooper
Bart
B
D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D011499:Protein Processing, Post-Translational; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases