Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30.
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.
Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
Chie
C
Ishikawa
Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
Masachika
M
Senba
Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
Naoki
N
Mori
D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism* / Q000821:virology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D020672:I-kappa B Proteins; D017730:Ki-1 Antigen; D016328:NF-kappa B; D014763:Viral Matrix Proteins