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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 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 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 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter via NF-B Liang Yu1, Abdalla J. Mohamed1, Oscar E. Simonson1, Leonardo Vargas1, K. Emelie M. Blomberg1, Bo Björkstrand2, H. Jose Arteaga1,3, Beston F. Nore1, and C. I. Edvard Smith1 1 Department of Laboratory Medicine, Clinical Research Center and 2 Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and 3 School of Medicine, Universidad Industrial de Santander, Bucaramanga, Colombia Bruton tyrosine kinase (Btk) is critical for B-cell development. Btk regulates a plethora of signaling proteins, among them nuclear factor-[]B (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, 2 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 autoregulatory 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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