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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3209-3217. Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-02-073957. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-073957v1 110/9/3209    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 Ekoff, M. Articles by Nilsson, G. Search for Related Content PubMed PubMed Citation Articles by Ekoff, M. Articles by Nilsson, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 21, 2007 Accepted July 5, 2007 The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells Maria Ekoff, Thomas Kaufmann, Maria Engstrom, Noboru Motoyama, Andreas Villunger, Jan-Ingvar Jonsson, Andreas Strasser, and Gunnar Nilsson* Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden Molecular Genetics of Cancer Division, the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia Division of Cell Biology, Dept. of Biomedicine & Surgery, Linkoping University, Linkoping, Sweden Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics & Gerontology, Obu, Japan Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria * Corresponding author; email: gunnar.p.nilsson{at}ki.se. Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical pro-apoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue-like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53-/- mast cells we found that cytokine deprivation-induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in Foxo3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation were markedly resistant to cytokine withdrawal compared to wild type cells. Moreover, overexpression of phosphorylation-deficient, constitutively active Foxo3a caused an upregulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation-induced mast cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. C. Cazanave, J. L. Mott, N. A. Elmi, S. F. Bronk, N. W. Werneburg, Y. Akazawa, A. Kahraman, S. P. Garrison, G. P. Zambetti, M. R. Charlton, et al. JNK1-dependent PUMA Expression Contributes to Hepatocyte Lipoapoptosis J. Biol. Chem., September 25, 2009; 284(39): 26591 - 26602. [Abstract] [Full Text] [PDF] T. R. Hercus, D. Thomas, M. A. Guthridge, P. G. Ekert, J. King-Scott, M. W. Parker, and A. F. Lopez The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease Blood, August 13, 2009; 114(7): 1289 - 1298. [Abstract] [Full Text] [PDF] C. Liu, D. Xu, L. Liu, F. Schain, A. Brunnstrom, M. Bjorkholm, H.-E. Claesson, and J. Sjoberg 15-Lipoxygenase-1 induces expression and release of chemokines in cultured human lung epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L196 - L203. [Abstract] [Full Text] [PDF] N. D. Huntington, V. Labi, A. Cumano, P. Vieira, A. Strasser, A. Villunger, J. P. Di Santo, and N. L. Alves Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim sustains B lymphopoiesis in the absence of IL-7 Int. Immunol., June 1, 2009; 21(6): 715 - 725. [Abstract] [Full Text] [PDF] Y. Zhao, J. L. Coloff, E. C. Ferguson, S. R. Jacobs, K. Cui, and J. C. Rathmell Glucose Metabolism Attenuates p53 and Puma-dependent Cell Death upon Growth Factor Deprivation J. Biol. Chem., December 26, 2008; 283(52): 36344 - 36353. [Abstract] [Full Text] [PDF] S. A. Didichenko, N. Spiegl, T. Brunner, and C. A. Dahinden IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils Blood, November 15, 2008; 112(10): 3949 - 3958. [Abstract] [Full Text] [PDF]

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