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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2121-2127. Prepublished online as a Blood First Edition Paper on June 13, 2007; DOI 10.1182/blood-2007-02-073080. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-073080v1 110/6/2121    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 Zhou, H.-J. Articles by Ford, R. J. Search for Related Content PubMed PubMed Citation Articles by Zhou, H.-J. Articles by Ford, R. J. Related Collections Neoplasia Cell Cycle Oncogenes and Tumor Suppressors Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma Hai-Jun Zhou1, Lan V. Pham1, Archito T. Tamayo1, Yen-Chiu Lin-Lee1, Lingchen Fu1, Linda C. Yoshimura1, and Richard J. Ford1 1 Department of Hematopathology, the University of Texas M. D. Anderson Cancer Center, Houston CD40 is an integral plasma membrane–associated member of the TNF receptor family that has recently been shown to also reside in the nucleus of both normal B cells and large B-cell lymphoma (LBCL) cells. However, the physiological function of CD40 in the B-cell nucleus has not been examined. In this study, we demonstrate that nuclear CD40 interacts with the NF-B protein c-Rel, but not p65, in LBCL cells. Nuclear CD40 forms complexes with c-Rel on the promoters of NF-B target genes, CD154, BLyS/BAFF, and Bfl-1/A1, in various LBCL cell lines. Wild-type CD40, but not NLS-mutated CD40, further enhances c-Rel–mediated Blys promoter activation as well as proliferation in LBCL cells. Studies in normal B cells and LBCL patient cells further support a nuclear transcriptional function for CD40 and c-Rel. Cooperation between nuclear CD40 and c-Rel appears to be important in regulating cell growth and survival genes involved in lymphoma cell proliferation and survival mechanisms. Modulating the nuclear function of CD40 and c-Rel could reveal new mechanisms in LBCL pathophysiology and provide potential new targets for lymphoma therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CD40 promotes lymphoma from nuclear hideaway Davide Rossi and Gianluca Gaidano Blood 2007 110: 1710-1711. [Full Text] [PDF] This article has been cited by other articles: S.-H. Kuo, P.-Y. Yeh, L.-T. Chen, M.-S. Wu, C.-W. Lin, K.-H. Yeh, Y.-S. Tzeng, J.-Y. Chen, P.-N. Hsu, J.-T. Lin, et al. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma Blood, October 1, 2008; 112(7): 2927 - 2934. [Abstract] [Full Text] [PDF] L. V. Pham, H.-J. Zhou, Y.-C. Lin-Lee, A. T. Tamayo, L. C. Yoshimura, L. Fu, B. G. Darnay, and R. J. Ford Nuclear Tumor Necrosis Factor Receptor-associated Factor 6 in Lymphoid Cells Negatively Regulates c-Myb-mediated Transactivation through Small Ubiquitin-related Modifier-1 Modification J. Biol. Chem., February 22, 2008; 283(8): 5081 - 5089. [Abstract] [Full Text] [PDF]

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