A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b.

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Citation

Fluhrer R, Grammer G, Israel L, Condron MM, Haffner C, Friedmann E, Bohland C, Imhof A, Martoglio B, Teplow DB, Haass C

A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b.

Nat Cell Biol. 2006 Aug;8(8):894-6. Epub 2006 Jul 9.

PubMed ID
16829951 [ View in PubMed
]
Abstract

Gamma-secretase and signal peptide peptidase (SPP) are unusual GxGD aspartyl proteases, which mediate intramembrane proteolysis. In addition to SPP, a family of SPP-like proteins (SPPLs) of unknown function has been identified. We demonstrate that SPPL2b utilizes multiple intramembrane cleavages to liberate the intracellular domain of tumor necrosis factor alpha (TNFalpha) into the cytosol and the carboxy-terminal counterpart into the extracellular space. These findings suggest common principles for regulated intramembrane proteolysis by GxGD aspartyl proteases.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tumor necrosis factorP01375Details