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A γ-secretase-like intramembrane cleavage of TNFα by the GxGD aspartyl protease SPPL2b
- Fluhrer, Regina;
- Grammer, Gudula;
- Israel, Lars;
- Condron, Margaret M;
- Haffner, Christof;
- Friedmann, Elena;
- Böhland, Claudia;
- Imhof, Axel;
- Martoglio, Bruno;
- Teplow, David B;
- Haass, Christian
Published Web Location
https://doi.org/10.1038/ncb1450Abstract
Abstractγ-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 α (TNFα) 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.
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