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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases / genetics
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Aspartic Acid Endopeptidases / metabolism*
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Binding Sites / genetics
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Cell Line
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Cytosol / chemistry
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Cytosol / enzymology
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Cytosol / metabolism
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Endopeptidases / metabolism*
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Humans
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Intracellular Membranes / metabolism*
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Molecular Sequence Data
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Mutation / genetics
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Tumor Necrosis Factor-alpha / chemistry
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism*
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Tumor Necrosis Factor-alpha
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Zebrafish Proteins
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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signal peptide peptidase
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sppl2 protein, zebrafish
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BACE1 protein, human