Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma

Hai Jun Zhou, Lan V. Pham, Archito T. Tamayo, Yen Chiu Lin-Lee, Lingchen Fu, Linda C. Yoshimura, Richard J. Ford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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-κB protein c-Rel, but not p65, in LBCL cells. Nuclear CD40 forms complexes with c-Rel on the promoters of NF-κB 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.

Original languageEnglish (US)
Pages (from-to)2121-2127
Number of pages7
JournalBlood
Volume110
Issue number6
DOIs
StatePublished - Sep 15 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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