HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 24, 17475-17485, June 15, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/24/17475    most recent M607313200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mineva, N. D. Articles by Sonenshein, G. E. Search for Related Content PubMed PubMed Citation Articles by Mineva, N. D. Articles by Sonenshein, G. E. Social Bookmarking                      What's this?

CD40 Ligand-mediated Activation of the de Novo RelB NF-B Synthesis Pathway in Transformed B Cells Promotes Rescue from Apoptosis^*

Nora D. Mineva, Thomas L. Rothstein, John A. Meyers, Adam Lerner, and Gail E. Sonenshein^¶1

From the Departments of Pathology and Laboratory Medicine, Medicine, and ^¶Biochemistry, Boston University Medical School, Boston, Massachusetts 02118

CD40, a tumor necrosis factor receptor family member, is expressed on B lymphocytes. Interaction between CD40 and its ligand (CD40L), expressed on activated T lymphocytes, is critical for B cell survival. Here, we demonstrate that CD40 signals B cell survival in part via transcriptional activation of the RelB NF-B subunit. CD40L treatment of chronic lymphocytic leukemia cells induced levels of relB mRNA. Similarly, CD40L-mediated rescue of WEHI 231 B lymphoma cells from apoptosis induced upon B cell receptor (surface IgM) engagement led to increased relB mRNA levels. Recently, we characterized a new de novo synthesis pathway for the RelB NF-B subunit, induced by the cytomegalovirus IE1 protein, in which binding of p50/p65 NF-B and c-Jun/Fra-2 AP-1 complexes to the relB promoter works in synergy to potently activate transcription (Wang, X., and Sonenshein, G. E. (2005) J. Virol. 79, 95–105). CD40L treatment of WEHI 231 cells caused induction of AP-1 family members Fra-2, c-Jun, JunD, and JunB. Cotransfection of Fra-2 with the Jun AP-1 subunits and p50/c-Rel NF-B led to synergistic activation of the relB promoter. Ectopic expression of relB or RelB knockdown using small interfering RNA demonstrated the important role of this subunit in control of WEHI 231 cell survival and implicated activation of the anti-apoptotic factors Survivin and manganese superoxide dismutase. Thus, CD40 engagement of transformed B cells activates relB gene transcription via a process we have termed the de novo RelB synthesis pathway, which protects these cells from apoptosis.

Received for publication, August 2, 2006 , and in revised form, April 18, 2007.

^* This work was supported by National Institutes of Health Grants RO1 CA36355 (to G. E. S.) and RO1 AI40181 (to T. L. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biochemistry, Boston University School of Medicine, 715 Albany St., Boston, MA 02118. Tel.: 617-638-4120; Fax: 617-638-4252; E-mail: gsonensh{at}bu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. J. Baglole, S. B. Maggirwar, T. A. Gasiewicz, T. H. Thatcher, R. P. Phipps, and P. J. Sime The Aryl Hydrocarbon Receptor Attenuates Tobacco Smoke-induced Cyclooxygenase-2 and Prostaglandin Production in Lung Fibroblasts through Regulation of the NF-{kappa}B Family Member RelB J. Biol. Chem., October 24, 2008; 283(43): 28944 - 28957. [Abstract] [Full Text] [PDF]

				S. M. Shahjahan Miah, T. L. Hughes, and K. S. Campbell KIR2DL4 Differentially Signals Downstream Functions in Human NK Cells through Distinct Structural Modules J. Immunol., March 1, 2008; 180(5): 2922 - 2932. [Abstract] [Full Text] [PDF]

				Y. Dai, S. Chen, L. B. Kramer, V. L. Funk, P. Dent, and S. Grant Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells Clin. Cancer Res., January 15, 2008; 14(2): 549 - 558. [Abstract] [Full Text] [PDF]