BCL-6 negatively regulates expression of the NF-κB1 p105/p50 subunit

Zhiping Li, Xing Wang, Raymond Yick Loi Yu, B. Belinda Ding, J. Jessica Yu, Xu Ming Dai, Akira Naganuma, E. Richard Stanley, B. Hilda Ye

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

BCL-6 is a transcription repressor frequently deregulated in non-Hodgkin's B cell lymphomas. Its activity is also critical to germinal center development and balanced Th1/Th2 differentiation. Previous studies have suggested that NF-κB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown. We report in this study that BCL-6 can bind to three sequence motifs in the 5′ regulatory region of NF-κB1 in vitro and in vivo, and repress NF-κB1 transcription both in reporter assays and in lymphoma B cell lines. BCL-6 -/- mice further confirm the biological relevance of BCL-6-dependent regulation of NF-κB1 because BCL-6 inactivation caused notable increase in p105/p50 proteins in several cell types. Among these, BCL-6-/- macrophage cell lines displayed a hyperproliferation phenotype that can be reversed by NF-κB inhibitors, e.g., N-tosyl-L-phenylalanine chloromethyl ketone and SN50, a result that is consistent with increased nuclear κB-binding activity of p50 homodimer and p50/p65 heterodimer. Our results demonstrate that BCL-6 can negatively regulate NF-κB1 expression, thereby inhibiting NF-κB-mediated cellular functions. The Journal of Immunology, 2005, 174: 205-214.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalJournal of Immunology
Volume174
Issue number1
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Li, Z., Wang, X., Yu, R. Y. L., Ding, B. B., Yu, J. J., Dai, X. M., Naganuma, A., Stanley, E. R., & Ye, B. H. (2005). BCL-6 negatively regulates expression of the NF-κB1 p105/p50 subunit. Journal of Immunology, 174(1), 205-214.