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* Integrated Department of Immunology, and
Department of Pediatrics, and
Department of Pharmacology,
Department of Medicine, and
¶ Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262;
|| Howard Hughes Medical Institute, and
# Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206
The life and death of T cells is controlled to a large extent by the relative amounts of Bcl-2-related proteins they contain. The antiapoptotic protein Bcl-2 and the proapoptotic protein Bim are particularly important in this process with the amount of Bcl-2 per cell dropping by about one-half when T cells prepare to die. In this study we show that Bcl-2 and Bim each control the expression of the other. Absence of Bim leads to a drop in the amount of intracellular Bcl-2 protein, while having no effect on the amounts of mRNA for Bcl-2. Conversely, high amounts of Bcl-2 per cell allow high amounts of Bim, although in this case the effect involves increases in Bim mRNA. These mutual effects occur even if Bcl-2 is induced acutely. Thus these two proteins control the expression of the other, at either the protein or mRNA level.
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1 This work was supported in part by a National Institute of Child Health and Human Development Award K12-HD00850 (to M.W.). This work was also supported by Grants AI-17134, AI-18785, and AI-22295 from the U.S. Public Health Service, by Grant AI-002 from the Autoimmunity Center of Excellence, and by Grant CA-046934 from the Cancer Center Core Funding (to P.M. and J.W.K.). This work is supported by Grant CA-117802 from the U.S. Public Health Service and by a Translational Research Award from the Leukemia and Lymphoma Society (to Y.R.). M.W. is a National Institute of Child Health and Human Development Fellow of the Pediatric Scientist Development Program.
2 T.N.J., A.M., and M.W. contributed equally to the work.
3 Address correspondence and reprint requests to Dr. Philippa Marrack, Integrated Department of Immunology, Howard Hughes Medical Institute, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: marrackp{at}njc.org
4 Abbreviations used in this paper: hBcl-2, human Bcl-2; mBcl-2, mouse Bcl-2; MMTV, mouse mammary tumor virus.
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