Abstract
Drosophila genes reaper, grim, and head-involution-defective (hid) induce apoptosis in several cellular contexts. N-terminal sequences of these proteins are highly conserved and are similar to N-terminal inactivation domains of voltage-gated potassium (K+) channels. Synthetic Reaper and Grim N terminus peptides induced fast inactivation of Shaker-type K+ channels when applied to the cytoplasmic side of the channel that was qualitatively similar to the inactivation produced by other K+ channel inactivation particles. Mutations that reduce the apoptotic activity of Reaper also reduced the synthetic peptide's ability to induce channel inactivation, indicating that K+ channel inactivation correlated with apoptotic activity. Coexpression of Reaper RNA or direct injection of full length Reaper protein caused near irreversible block of the K+ channels. These results suggest that Reaper and Grim may participate in initiating apoptosis by stably blocking K+ channels.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / genetics
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Apoptosis / physiology*
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Base Sequence
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DNA Primers / genetics
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Drosophila / cytology
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Drosophila / genetics
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Drosophila / metabolism
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Drosophila Proteins*
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Female
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Genes, Insect
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Insect Proteins / genetics
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Insect Proteins / metabolism
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Molecular Sequence Data
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Mutation
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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Oocytes / metabolism
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Peptides / genetics
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Peptides / metabolism*
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Potassium Channel Blockers
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Shaker Superfamily of Potassium Channels
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Xenopus
Substances
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DNA Primers
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Drosophila Proteins
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Insect Proteins
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Neuropeptides
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Peptide Fragments
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Peptides
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Potassium Channel Blockers
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Potassium Channels
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Recombinant Proteins
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Sh protein, Drosophila
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Shaker Superfamily of Potassium Channels
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grim protein, Drosophila
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rpr protein, Drosophila