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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4617-4626. Prepublished online as a Blood First Edition Paper on February 21, 2008; DOI 10.1182/blood-2007-10-121137. This Article Full Text (PDF) All Versions of this Article: blood-2007-10-121137v1 111/9/4617    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 Yu, L. Articles by Smith, C. I. E. Search for Related Content PubMed PubMed Citation Articles by Yu, L. Articles by Smith, C. I. E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 31, 2007 Accepted February 13, 2008 Proteasome dependent auto-regulation of Bruton's tyrosine kinase (Btk) promoter via NF-B Liang Yu*, Abdalla J. Mohamed, Oscar E. Simonson, Leonardo Vargas, K. Emelie M. Blomberg, Bo Bjorkstrand, H. Jose Arteaga, Beston F. Nore, and C. I. Edvard Smith Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden School of Medicine, Universidad Industrial de Santander, Bucaramanga, Colombia * Corresponding author; email: liang.yu{at}ki.se. Bruton's tyrosine kinase (Btk) is critical for B cell development. Btk regulates a plethora of signaling proteins, among them NF-B. Activation of NF-B is a hallmark of B cells, and NF-B signaling is severely compromised in Btk deficiency. We here present strong evidence indicating that NF-B is required for efficient transcription of the Btk gene. First, we found that proteasome blockers and inhibitors of NF-B signaling suppress Btk transcription and intracellular expression. Similar to Btk, proteasome inhibitors also reduced the expression of other members of this family of kinases, Itk, Bmx and Tec. Second, two functional NF-B binding sites were found in the Btk promoter. Moreover, in live mice, by hydrodynamic transfection, we show that Bortezomib (a blocker of proteasomes and NF-B signaling), as well as NF-B binding sequence-oligonucleotide decoys block Btk transcription. We also demonstrate that Btk induces NF-B activity in mice. Collectively, we show that Btk uses a positive auto-regulatory feedback mechanism to stimulate transcription from its own promoter via NF-B. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. N. Khan B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis J. Immunol., September 15, 2009; 183(6): 3561 - 3567. [Abstract] [Full Text] [PDF] D. Y. H. Hallaert, A. Jaspers, C. J. van Noesel, M. H. J. van Oers, A. P. Kater, and E. Eldering c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches Blood, December 15, 2008; 112(13): 5141 - 5149. [Abstract] [Full Text] [PDF] C. Spatuzza, M. Schiavone, E. Di Salle, E. Janda, M. Sardiello, G. Fiume, O. Fierro, M. Simonetta, N. Argiriou, R. Faraonio, et al. Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk Nucleic Acids Res., August 1, 2008; 36(13): 4402 - 4416. [Abstract] [Full Text] [PDF]

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