Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans

Article Abstract:

Regulated intramembrane proteolysis (Rip), a control mechanism, is discussed in this review article. The mechanism is conserved from bacteria to humans. Conceptual convergence is now seen in the cell signaling field. Transmembrane proteins can be cleaved within the plane of the membrane of the cell to let out cytosolic fragments. The fragments can go into the nucleus to manage gene transcription. The mechanism is called Rip. Five proteins known or thought to undergo Rip in animal cells are SREBP, APP, Notch, Ire1 and ATF6, and there are two in bacteria.

Cellular signal transduction, Cytochemistry, Homology (Biology), Cellular control mechanisms, Cell regulation, Cell membranes, Plasma membranes

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Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment

Article Abstract:

The mechanism of release of sterol regulatory element binding proteins (SREBPs) from the endoplasmic reticulum membranes is a complex two-stage process. The first step, involving a cleavage near or at the Arg-519 in the lumenal loop, produces an intermediate of SREBP-2 that is membrane-bound. The cleavage is regulated by sterols. The second cleavage which is independent of sterols takes place within the transmembrane region. The second cleavage liberates the NH2-terminal mature form of SREBP-2 which translocates to the nucleus.

Analysis, Sterols

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Transport-dependent proteolysis of SREBP: relocation of Site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi

Article Abstract:

Results demonstrate that active domains of sterol regulatory element binding proteins (SREBPs) complexing with SREBP cleavage-activating protein (SCAP) carries the former from endoplasm reticulum to Golgi and are cleaved by Site-1 protease (S1P). The data suggest that shifting S1P from Golgi to endoplasm reticulum obviates this pathway for SREBP.

Golgi apparatus, Cholesterol metabolism

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