Regulated Intramembrane Proteolysis

Regulated intramembrane proteolysis (RIP) is a mechanism for signal transduction that involves the generation of regulatory molecules from membrane proteins through proteolytic cleavage. Such cleavage liberates cytoplasmic or lumenal/extracellular fragments from transmembrane precursor proteins, allowing the cleaved fragments to function at a new location. RIP influences processes as diverse as cellular differentiation, lipid metabolism, immune defense, and the response to unfolded proteins. Proteins that are known to undergo RIP span the membrane bilayer at least once. The intramembrane cleavage of RIP is mediated by four different families of membrane-bound proteases: Site-2 protease (S2P), γ-Secretase, Signal peptide peptidase (SPP), and Rhomboid. In addition to its occurrence in animal cells, RIP has been observed in lower organism including bacteria, and, remarkably, the bacterial proteases are related evolutionarily to the ones used in animal cells.