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This Article Full Text Full Text (PDF) 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 Annunziata, C. M. Articles by Cossman, J. Search for Related Content PubMed PubMed Citation Articles by Annunziata, C. M. Articles by Cossman, J. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2000, Vol. 96, No. 8, pp. 2841-2848 NEOPLASIA Hodgkin disease: pharmacologic intervention of the CD40-NFB pathway by a protease inhibitor Christina M. Annunziata, Yassamin J. Safiran, Steven G. Irving, Usha N. Kasid, and Jeffrey Cossman From Georgetown University Medical Center, Washington, DC. The malignant Reed-Sternberg cell of Hodgkin disease is an aberrant B cell that persists in an immunolgically mediated inflammatory infiltrate. Despite its nonproductive immunoglobulin genes, the Reed-Sternberg cell avoids the usual apoptotic fate of defective immune cells through an unknown mechanism. A likely candidate is the surface receptor, CD40, consistently expressed by Reed-Sternberg cells, and the first link in the pathway to NF-B activation, the central regulator of cytokine production and apoptosis. CD40 signaling in B lymphocytes coordinates the immune response, including immunoglobulin isotype switch and Fas-mediated apoptosis. CD40-induced NF-B activation is mediated by adapter proteins, the TNF receptor (TNFR)-associated factors (TRAFs), especially TRAFs 2, 3, and 5. Using a Hodgkin cell line, this study demonstrates that CD40 activation of NF-B is mediated by proteolysis of TRAF3. Results further demonstrate that the pathway can be blocked by treatment with pharmacologic doses of a specific protease inhibitor, pepstatin-A, even in the presence of a mutated NF-B inhibitor, I-B. The stability of TRAF3 regulates CD40/NF-B-mediated control of the immune response, which is central to the biologic activity of the Reed-Sternberg cell. Prevention of TRAF3 proteolysis may be an entry point for design of novel pharmaceuticals to treat Hodgkin disease and immune system disorders. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Chiu, W. Xu, B. He, S. R. Dillon, J. A. Gross, E. Sievers, X. Qiao, P. Santini, E. Hyjek, J.-w. Lee, et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL Blood, January 15, 2007; 109(2): 729 - 739. [Abstract] [Full Text] [PDF] H. 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