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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References
Adams JM, Cory S . 1998 Science 281: 1322–1326
Boise LH, González-García M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB . 1993 Cell 74: 597–608
Cerezo A, Martinez-AC, Gonzalez A, Gómez J, Rebollo A . 1999 Cell Death Differ. 6: 87–94
Cerezo A, Martinez AC, Lanzarot D, Fischer S, Franke TF, Rebollo A . 1998 Mol. Biol. Cell. 8: 3107–3118
Chittenden T, Flemington C, Houghton AB, Ebb GC, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ . 1995b EMBO J. 14: 5589–5596
Chinttenden T, Harrington EA, O'Connor R, Flemington C, Lutz RJ, Evan GI, Guild C . 1995a Nature 374: 733–736
Datta SR, Dukek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME . 1997 Cell 91: 231–239
Del Peso L, Garcia MG, Page C, Herrera R, Nuñez G . 1997 Science 278: 687–694
Deleersnijder W, Hong G, Cortvrindt R, Poirier C, Tylzanowski P, Pittois K, Van Mark E, Merregaert J . 1996 J. Biol. Chem. 271: 19475–19482
Fesik SW . 2000 Cell 103: 273–282
Ghosh A, Sankar SN, Rowe RM, Sen GC . 2001 J. Biol. Chem. 276: 25447–25455
Gross A, McDonnell JM, Korsmeyer SJ . 1999 Genes Dev. 13: 1899–1911
Han J, Sabbatini P, White E . 1996 Mol. Cell. Biol. 16: 5857–5864
Hsu HY, Kaipai L, Zhu L, Hsueh AJ . 1997 Mol. Endocrinol. 11: 1858–1866
Hubank M, Schatz DG . 1994 Nucleic Acids Res. 22: 5640–5648
Kelekar A, Thompson CB . 1998 Trends Cell Biol. 8: 324–330
Louahed J, Grasso L, De Smet C, Van Roost E, Wildmann C, Nicolaides NC, Levitt RC, Renauld JC . 1999 Blood 94: 1701–1709
Lutz RJ . 2000 Biochem. Society Trans. 28: 51–55
Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N . 2000 Science 288: 1053–1058
Pitton C, Rebollo A, Van Snick J, Theze J, Garcia A . 1993 Cytokine 5: 362–368
Rebollo A, Dumoutier L, Renauld JC, Zaballos A, Ayllón V, Martinez-AC . 2000 Mol. Cell. Biol. 20: 3407–3416
Romero F, Martinez AC, Camonis J, Rebollo A . 1999 EMBO J. 18: 3419–3430
Simonain PL, Grillot DA, Merino R, Nuñez G . 1996 J. Biol. Chem. 271: 22764–22772
Wang K, Gross A, Waksman G, Korsmeyer SJ . 1998 Mol. Cell. Biol. 18: 6083–6089
Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ . 2000 Genes Dev. 14: 2060–2071
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TJ, Jones DP, Wang X . 1997 Science 275: 1129–1132
Zha H, Aime-Sempe C, Sato T, Reed JC . 1996a J. Biol. Chem. 271: 7440–7444
Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ . 1996b Cell 87: 619–629
Zha J, Weiller S, Joon K, Wei MC, Korsmeyer SJ . 2000 Science 290: 1761–1765
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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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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DOI: https://doi.org/10.1038/sj.onc.1205464
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