Submitted May 15, 2006
Accepted October 21, 2006
BMI-1 is induced by the Epstein-Barr virus oncogene LMP1, and regulates the expression of viral target genes in Hodgkin's lymphoma cells
Amanda Dutton, Ciaran B Woodman, Marilyn B Chukwuma, James IK Last, Wenbin Wei, Martina Vockerodt, Karl RN Baumforth, Joanne R Flavell, Martin Rowe, A. Malcolm R Taylor, Lawrence S Young, and Paul G Murray*
The Medical School, University of Birmingham, United Kingdom
* Corresponding author; email: p.g.murray{at}bham.ac.uk.
Polycomb Group (PcG) proteins are chromatin modifiers which are necessary for the maintenance and renewal of embryonic and adult stem cells. However, over-expression of the PcG protein, Bmi-1, causes lymphomas in transgenic mice. We show that Bmi-1 is upregulated in Hodgkin's lymphoma (HL) cells by the Epstein-Barr virus oncogene, latent membrane protein-1 (LMP1), and that this upregulation is mediated by NF-
B signalling; we also show that Bmi-1 is upregulated by NF-B in EBV-negative HL cells. Downregulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the pro-survival effects of LMP1-induced NF-B signalling in HL cells. Transcriptional targets of Bmi-1 were identified following its knockdown in a HL cell line. We show here that both Bmi-1 and LMP1 downregulate the ataxia telangiectasia mutated (ATM) tumor suppressor. We conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
