Proapoptotic activity of ITM2B(s), a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2.
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.
Fleischer
Aarne
A
Department of Immunology and Oncology,Centro Nacional de Biotecnología, Campus de Cantoblanco, UAM, 28049 Madrid, Spain.
Ayllón
Verónica
V
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Rebollo
Angelita
A
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013382:Subtraction Technique; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D051025:bcl-Associated Death Protein
D048868:Adaptor Proteins, Signal Transducing; C494820:Bad protein, mouse; D002352:Carrier Proteins; D007376:Interleukin-2; C492300:Itm2b protein, mouse; D046911:Macromolecular Substances; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051025:bcl-Associated Death Protein