Deleted in breast cancer 1 suppresses B cell activation through RelB and is regulated by IKKα phosphorylation

Sinyi Kong, Hongxin Dong, Jianxun Song, Muthusamy Thiruppathi, Bellur S. Prabhakar, Quan Qiu, Zhenghong Lin, Eduardo Chini, Bin Zhang, Deyu Fang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Alternative NF-κB signaling is crucial for B cell activation and Ig production, and it is mainly regulated by the inhibitor of κ B kinase (IKK) regulatory complex. Dysregulation of alternative NF-κB signaling in B cells could therefore lead to hyperactive B cells and Ig overproduction. In our previous, study we found that deleted in breast cancer 1 (DBC1) is a suppressor of the alternative NF-κB pathway to attenuate B cell activation. In this study, we report that loss of DBC1 results in spontaneous overproduction of Ig in mice after 10 mo of age. Using a double mutant genetic model, we confirm that DBC1 suppresses B cell activation through RelB inhibition. At the molecular level, we show that DBC1 interacts with alternative NF-κB members RelB and p52 through its leucine zipper domain. In addition, phosphorylation of DBC1 at its C terminus by IKKα facilitates its interaction with RelB and IKKα, indicating that DBC1-mediated suppression of alternative NF-κB is regulated by IKKα. Our results define the molecular mechanism of DBC1 inhibition of alternative NF-κB activation in suppressing B cell activation.

Original languageEnglish (US)
Pages (from-to)3685-3693
Number of pages9
JournalJournal of Immunology
Volume195
Issue number8
DOIs
StatePublished - Oct 15 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Kong, S., Dong, H., Song, J., Thiruppathi, M., Prabhakar, B. S., Qiu, Q., Lin, Z., Chini, E., Zhang, B., & Fang, D. (2015). Deleted in breast cancer 1 suppresses B cell activation through RelB and is regulated by IKKα phosphorylation. Journal of Immunology, 195(8), 3685-3693. https://doi.org/10.4049/jimmunol.1500713