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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3081-3089. Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2006-10-053371. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-053371v1 111/6/3081    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 Ulleras, E. Articles by Nilsson, G. Search for Related Content PubMed PubMed Citation Articles by Ulleras, E. Articles by Nilsson, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 24, 2006 Accepted December 17, 2007 NFAT but not NF-B is critical for transcriptional induction of the pro-survival gene A1 following IgE receptor activation in mast cells Erik Ulleras, Mats Karlberg, Christine Moller Westerberg, Jessica Alfredsson, Steve Gerondakis, Andreas Strasser, and Gunnar Nilsson* Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden The Walter and Eliza Hall Institute, Melbourne, Australia * Corresponding author; email: gunnar.p.nilsson{at}ki.se. FcRI-activation-induced survival of mast cells is dependent on the expression and function of the pro-survival protein A1. The expression of A1 in lymphocytes and monocytes has previously been described to be transcriptionally regulated by NF-B. Here we demonstrate that the expression of A1 in mast cells is not dependent on NF-B, but that NFAT plays a crucial role. FcRI-induced A1 expression was not affected in mast cells over-expressing an IB- super-repressor, or cells lacking NF-B subunits RelA, c-Rel or c-Rel plus NF-B1 p50. In contrast, inhibition of calcineurin and NFAT by cyclosporin A abrogated the expression of A1 in mast cells upon FcRI-activation, but had no effect on LPS-induced expression of A1 in J774A.1 monocytic cells. Cyclosporin A also inhibited luciferase expression in an A1 promoter reporter assay. A putative NFAT binding site in the A1 promoter showed inducible protein binding following FcRI crosslinking or treatment with ionomycin as detected in a band shift assay or chromatin immunoprecipitation. The binding protein was identified as NFAT1. Finally, mast cells expressing constitutively active NFAT1 exhibit increased expression of A1 after FcRI-stimulation. These results indicate that in FcRI stimulated mast cells, A1 is transcriptionally regulated by NFAT1 but not by NF-B. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. F. Andrews and D. J. Rawlings Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription J. Immunol., March 1, 2009; 182(5): 2868 - 2878. [Abstract] [Full Text] [PDF]

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