A γ-secretase-like intramembrane cleavage of TNFα by the GxGD aspartyl protease SPPL2b

9 July 2006

journal article
research article
Published by Springer Nature in Nature Cell Biology

Vol. 8 (8) , 894-896
https://doi.org/10.1038/ncb1450

Abstract

γ-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.

Keywords

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