Deleted in Breast Cancer 1 Suppresses B Cell Activation through RelB and Is Regulated by IKK Phosphorylation. Academic Article uri icon


  • Alternative NF-B signaling is crucial for B cell activation and Ig production, and it is mainly regulated by the inhibitor of B kinase (IKK) regulatory complex. Dysregulation of alternative NF-B 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-B 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-B members RelB and p52 through its leucine zipper domain. In addition, phosphorylation of DBC1 at its C terminus by IKK facilitates its interaction with RelB and IKK, indicating that DBC1-mediated suppression of alternative NF-B is regulated by IKK. Our results define the molecular mechanism of DBC1 inhibition of alternative NF-B activation in suppressing B cell activation.

published proceedings

  • J Immunol

altmetric score

  • 0.75

author list (cited authors)

  • Kong, S., Dong, H., Song, J., Thiruppathi, M., Prabhakar, B. S., Qiu, Q., ... Fang, D.

citation count

  • 10

complete list of authors

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

publication date

  • October 2015