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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 20, 2005 Accepted August 11, 2005 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* Division of Experimental Pathophysiology & Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia * Corresponding author; email: andreas.villunger{at}uibk.ac.at. Numerous p53-target genes have been implicated in DNA damage-induced apoptosis signaling, but pro-apoptotic Bcl-2 family members of the BH3-only subgroup appear to play the critical initiating role. In various types of cultured cells, three BH3-only proteins, namely Puma, Noxa and Bim, have been shown to initiate p53-dependent as well as p53-independent apoptosis in response to DNA damage or treatment with anti-cancer 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 bcl-2 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: R. S. Hotchkiss, A. Strasser, J. E. McDunn, and P. E. Swanson Cell Death N. Engl. J. Med., October 15, 2009; 361(16): 1570 - 1583. [Full Text] [PDF] A. J. Steele, A. G. Prentice, A. V. Hoffbrand, B. C. Yogashangary, S. M. Hart, M. W. Lowdell, E. R. Samuel, J. M. North, E. P. Nacheva, A. Chanalaris, et al. 2-phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells Blood, August 6, 2009; 114(6): 1217 - 1225. [Abstract] [Full Text] [PDF] E. H. Naderi, H. W. Findley, E. Ruud, H. K. Blomhoff, and S. 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