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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2891-2899. Prepublished online as a Blood First Edition Paper on December 14, 2004; DOI 10.1182/blood-2004-06-2297. This Article Full Text (PDF) All Versions of this Article: 2004-06-2297v1 105/7/2891    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 Ho, L. Articles by Schwaller, J. Search for Related Content PubMed PubMed Citation Articles by Ho, L. Articles by Schwaller, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 17, 2004 Accepted November 2, 2004 MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-B dependent proliferative advantage and resistance against FAS-induced cell death in B cells Liza Ho, R E Davis, Beatrice Conne, Richard Chappuis, Margaret Berczy, Paulette Mhawech, Louis M Staudt, and Juerg Schwaller* Department of Clinical Pathology, Geneva University Hospital, CMU, Geneva, Switzerland Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA * Corresponding author; email: juerg.schwaller{at}hcuge.ch. The most frequent recurring translocations in MALT B-cell Non-Hodgkin's lymphoma, t(11;18)(q21;q21) and t(14;18)(q32;q21), lead to formation of an API2-MALT1 fusion or IgH-mediated MALT1 over-expression. Various approaches have implicated these proteins in NF-B signaling, but this has not been shown experimentally in human B cells. Immunohistochemistry showed that MALT1 is predominantly expressed in normal and malignant germinal center B-cells, corresponding to the differentiation stage of MALT lymphoma. We expressed MALT1 and API2-MALT1 in human B-cell lymphoma BJAB cells, and found both transgenes in membrane lipid rafts along with endogenous MALT1 and two binding partners involved in NF-B signaling, BCL10 and CARMA1. API2-MALT1 and exogenous MALT1 increased constitutive NF-B activity and enhanced IKK activation induced by CD40 stimulation. Both transgenes protected BJAB cells from FAS-induced death, consistent with increases in NF-B cytoprotective target gene expression, and increased their proliferation rate. Expression of a dominant-negative IB mutant showed that these survival and proliferative advantages are dependent on elevated constitutive NF-B activity. Our findings support a model in which NF-B signaling, once activated in a CD40-dependent immune response, is maintained and enhanced through deregulation of MALT1 or formation of an API2-MALT1 fusion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. J. Bende, F. van Maldegem, and C. J.M. van Noesel Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas Haematologica, August 1, 2009; 94(8): 1109 - 1123. [Abstract] [Full Text] [PDF] J. Dierlamm, E. M. Murga Penas, S. Bentink, S. Wessendorf, H. Berger, M. Hummel, W. Klapper, D. Lenze, A. Rosenwald, E. Haralambieva, et al. Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma Haematologica, May 1, 2008; 93(5): 688 - 696. [Abstract] [Full Text] [PDF] G. Sethi, B. Sung, and B. B. Aggarwal Nuclear Factor-{kappa}B Activation: From Bench to Bedside Experimental Biology and Medicine, January 1, 2008; 233(1): 21 - 31. [Abstract] [Full Text] [PDF] H. Noels, G. van Loo, S. Hagens, V. Broeckx, R. Beyaert, P. Marynen, and M. Baens A Novel TRAF6 Binding Site in MALT1 Defines Distinct Mechanisms of NF-{kappa}B Activation by API2{middle dot}MALT1 Fusions J. Biol. Chem., April 6, 2007; 282(14): 10180 - 10189. [Abstract] [Full Text] [PDF] C. Van Waes Nuclear Factor-{kappa}B in Development, Prevention, and Therapy of Cancer Clin. Cancer Res., February 15, 2007; 13(4): 1076 - 1082. [Abstract] [Full Text] [PDF] M-Q Du and J C Atherton Molecular subtyping of gastric MALT lymphomas: implications for prognosis and management. Gut, June 1, 2006; 55(6): 886 - 893. [Full Text] [PDF] M. Baens, S. Fevery, X. Sagaert, H. Noels, S. Hagens, V. Broeckx, A. D. Billiau, C. De Wolf-Peeters, and P. Marynen Selective Expansion of Marginal Zone B Cells in E{micro}-API2-MALT1 Mice Is Linked to Enhanced I{kappa}B Kinase {gamma} Polyubiquitination. Cancer Res., May 15, 2006; 66(10): 5270 - 5277. [Abstract] [Full Text] [PDF]

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