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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4131-4138. Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-04-1595. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-04-1595v1 106/13/4131    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Erlacher, M. Articles by Villunger, A. Search for Related Content PubMed PubMed Citation Articles by Erlacher, M. Articles by Villunger, A. Related Collections Hematopoiesis and Stem Cells Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS BH3-only proteins Puma and Bim are rate-limiting for -radiation– and glucocorticoid-induced apoptosis of lymphoid cells in vivo Miriam Erlacher, Ewa M. Michalak, Priscilla N. Kelly, Verena Labi, Harald Niederegger, Leigh Coultas, Jerry M. Adams, Andreas Strasser, and Andreas Villunger From the Division of Experimental Pathophysiology & Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria; and The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Numerous p53 target genes have been implicated in DNA damage–induced apoptosis signaling, but proapoptotic Bcl-2 (B-cell leukemia 2) family members of the BH3 (Bcl-2 homolog region [BH] 3)–only subgroup appear to play the critical initiating role. In various types of cultured cells, 3 BH3-only proteins, namely Puma (p53 up-regulated modulator of apoptosis), Noxa, and Bim (Bcl-2 interacting mediator of cell death), have been shown to initiate p53-dependent as well as p53-independent apoptosis in response to DNA damage and treatment with anticancer drugs or glucocorticoids. In particular, the absence of Puma or Bim renders thymocytes and mature lymphocytes refractory to varying degrees to death induced in vitro by growth factor withdrawal, DNA damage, or glucocorticoids. To assess the in vivo relevance of these findings, we subjected mice lacking Puma, Noxa, or Bim to whole-body -radiation or the glucocorticoid dexamethasone and compared lymphocyte survival with that in wild-type and BCL2–transgenic mice. Absence of Puma or Bcl-2 overexpression efficiently protected diverse types of lymphocytes from the effects of -radiation in vivo, and loss of Bim provided lower but significant protection in most lymphocytes, whereas Noxa deficiency had no impact. Furthermore, both Puma and Bim were found to contribute significantly to glucocorticoid-induced killing. Our results thus establish that Puma and Bim are key initiators of -radiation– and glucocorticoid-induced apoptosis in lymphoid cells in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Labi, M. Erlacher, S. Kiessling, C. Manzl, A. Frenzel, L. O'Reilly, A. Strasser, and A. Villunger Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates {gamma} irradiation-induced thymic lymphoma development J. Exp. Med., March 17, 2008; 205(3): 641 - 655. [Abstract] [Full Text] [PDF] Z. Ji, F. C. Mei, B. H. Johnson, E. B. Thompson, and X. 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