Abstract
Ligand binding to receptors of the LIN-12/Notch family causes at least two proteolytic cleavages: one between the extracellular and transmembrane domains, and the other within the transmembrane domain. The transmembrane cleavage depends on Presenilin, a protein also required for transmembrane cleavage of beta-APP. Here, we have assayed the substrate requirements for Presenilin-dependent processing of Notch and other type I transmembrane proteins in vivo. We find that the Presenilin-dependent cleavage does not depend critically on the recognition of particular sequences in these proteins but rather on the size of the extracellular domain: the smaller the size, the greater the efficiency of cleavage. Hence, Notch, beta-APP, and perhaps other proteins may be targeted for Presenilin-mediated transmembrane cleavage by upstream processing events that sever the extracellular domain from the rest of the protein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans Proteins*
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Cytoplasm
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Drosophila
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Drosophila Proteins
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Dynamins
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Extracellular Space
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism
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HSP70 Heat-Shock Proteins / genetics
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Helminth Proteins / chemistry
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Helminth Proteins / genetics
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Helminth Proteins / metabolism
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Herpes Simplex Virus Protein Vmw65 / genetics
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Lac Operon
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Presenilin-1
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Protein Structure, Tertiary
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Receptors, Notch
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Transgenes / physiology
Substances
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Caenorhabditis elegans Proteins
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Drosophila Proteins
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HSP70 Heat-Shock Proteins
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Helminth Proteins
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Herpes Simplex Virus Protein Vmw65
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Lin-12 protein, C elegans
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Membrane Proteins
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N protein, Drosophila
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Presenilin-1
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Receptors, Notch
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GTP Phosphohydrolases
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Dynamins