γ-Secretase: A Catalyst of Alzheimer Disease and Signal Transduction

Regulated intramembrane proteolysis (RIP) and signal transduction. Signal transduction by RIP depends on the sequential proteolytic processing of an integral membrane protein. First, an extracytosolic cleavage (green scissors) is implemented, followed by an intramembrane cleavage (red scissors) that releases a cytosolic fragment (shown in red). Upon translocation into the nucleus, this fragment regulates nuclear metabolism, which may culminate in further signaling.