Abstract
Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. Here we report the identification, the cloning and characterization of ITM2B(s), a protein induced upon IL-2-deprivation. ITM2B(s), which shares the BH3 domain of Bcl-2 family members, is a cytoplasmic and mitochondrial protein. Expression of ITM2B(s) induces apoptosis in IL-2-stimulated cells, but not in IL-4-stimulated cells, while overexpression of the long form of the protein is not able to induce apoptosis. In IL-2-stimulated cells, ITM2B(s) interacts with the antiapoptotic protein Bcl-2, and does not interact with the proapoptotic Bad. Mutation of the critical L and D residues within the BH3 domain abolished the ability of ITM2B(s) to promote apoptosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Alternative Splicing
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Apoptosis / physiology*
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Carrier Proteins / metabolism
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Cell Line / drug effects
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Cell Line / metabolism
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Cloning, Molecular
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Gene Expression Profiling
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Gene Expression Regulation / drug effects
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Interleukin-2 / pharmacology*
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Macromolecular Substances
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Molecular Sequence Data
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Recombinant Fusion Proteins / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Subtraction Technique
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism*
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Transfection
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bcl-Associated Death Protein
Substances
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Adaptor Proteins, Signal Transducing
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Bad protein, mouse
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Carrier Proteins
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Interleukin-2
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Itm2b protein, mouse
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Macromolecular Substances
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Membrane Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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bcl-Associated Death Protein