Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 282, Issue 24, Pages 17475-17485Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M607313200
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- NCI NIH HHS [R01 CA36355] Funding Source: Medline
- NIAID NIH HHS [R01 AI40181] Funding Source: Medline
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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-kappa 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-kappa B subunit, induced by the cytomegalovirus IE1 protein, in which binding of p50/p65 NF-kappa 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-kappa 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.
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