Abstract
Members of the ICE/ced-3 gene family have been implicated as components of the cell death pathway. Based on similarities with the structural prototype interleukin-1 beta-converting enzyme (ICE), family members are synthesized as proenzymes that are proteolytically processed to form active heterodimeric enzymes. In this report, we describe a novel member of this growing gene family, ICE-LAP3, which is closely related to the death effector Yama/CPP32/Apopain. Pro-ICE-LAP3 is a 35-kDa protein localized to the cytoplasm and expressed in a variety of tissues and cell lines. Overexpression of a truncated version of ICE-LAP3 (missing the pro-domain) induces apoptosis in MCF7 breast carcinoma cells. Importantly, upon receipt of a death stimulus, endogenous ICE-LAP3 is processed to its subunit forms, suggesting a physiological role in cell death. This is the first report to demonstrate processing of a native ICE/ced-3 family member during execution of the death program and the first description of the subcellular localization of an ICE/ced-3 family member.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Base Sequence
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Breast Neoplasms
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins*
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Caspase 7
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Caspases*
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Cell Line
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Cysteine Endopeptidases*
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DNA Primers
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Female
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Fetus
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Gene Expression
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Helminth Proteins / chemistry*
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Helminth Proteins / metabolism
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Humans
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Molecular Sequence Data
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Multigene Family
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Polymerase Chain Reaction
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Protein Biosynthesis
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Protein Precursors / biosynthesis
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Protein Precursors / metabolism
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Proteins / chemistry*
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Proteins / metabolism*
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Rats
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology*
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fas Receptor / pharmacology*
Substances
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Caenorhabditis elegans Proteins
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DNA Primers
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Helminth Proteins
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Protein Precursors
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Proteins
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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fas Receptor
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CASP7 protein, human
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Caspase 7
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Caspases
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Cysteine Endopeptidases
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ced-3 protein, C elegans