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Proapoptotic activity of ITM2Bs, a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2

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 ITM2Bs, a protein induced upon IL-2-deprivation. ITM2Bs, which shares the BH3 domain of Bcl-2 family members, is a cytoplasmic and mitochondrial protein. Expression of ITM2Bs 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, ITM2Bs 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 ITM2Bs to promote apoptosis.

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Acknowledgements

This work was partially supported by grants from Association pour la Recherche sur le Cancer (ARC), Dirección General de Investigación y Ciencia (DGIyC), Belgian Federal Service for Scientific, Technical and Cultural Affairs and Actions de Recherche Concertées, Direction de la Recherche Scientific. The Department of Immunology and Oncology was founded and is supported by the Spanish Research Council (CSIC) and Pharmacia Corporation.

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Correspondence to Angelita Rebollo.

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Fleischer, A., Ayllón, V., Dumoutier, L. et al. Proapoptotic activity of ITM2Bs, a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2. Oncogene 21, 3181–3189 (2002). https://doi.org/10.1038/sj.onc.1205464

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