Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30

Ishikawa,Chie; Senba,Masachika; Mori,Naoki

doi:10.3892/ijo.2015.3218

Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30

Authors:
- Chie Ishikawa
- Masachika Senba
- Naoki Mori
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Affiliations: Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
Published online on: October 22, 2015 https://doi.org/10.3892/ijo.2015.3218
Pages: 2197-2207

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Abstract

Activation of nuclear factor-κB (NF-κB) in Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL) cells is important in the transformation and development process of these lymphomas. Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and ligand-independent signaling by overexpressed CD30 are known to cause permanent activation of NF-κB in lymphomas. However, hyperactivation of NF-κB triggers cellular senescence and apoptosis. Here, we show that IκB-ζ, an inducible regulator of NF-κB, is constitutively expressed in BL and HL cell lines. In addition, immunohistochemical staining identified nuclear IκB-ζ‑positive BL cells, and Hodgkin and Reed-Sternberg cells in lymph nodes. Expression of LMP-1 and CD30 increased IκB-ζ expression at the transcriptional level. IκB-ζ promoter was regulated by activation of the NF-κB‑inducing kinase (NIK)/IκB kinase/NF-κB pathway via the carboxyl‑terminal tumor necrosis factor (TNF) receptor‑associated factor (TRAF)-interacting regions of LMP-1 and CD30. Interestingly, IκB-ζ inhibited NF-κB activation by LMP-1 and CD30. The results suggest that NF-κB-induced IκB-ζ negatively modulates NF-κB hyperactivation, resulting in a fine balance that ultimately endows a net evolutionary benefit to the survival of BL and HL cells.

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