1. Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells.
- Author
-
Dutton A, Woodman CB, Chukwuma MB, Last JI, Wei W, Vockerodt M, Baumforth KR, Flavell JR, Rowe M, Taylor AM, Young LS, and Murray PG
- Subjects
- Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Line, Cell Survival, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Down-Regulation, Gene Expression Profiling, Hodgkin Disease genetics, Hodgkin Disease pathology, Humans, NF-kappa B metabolism, Nuclear Proteins genetics, Polycomb Repressive Complex 1, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins genetics, Repressor Proteins genetics, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Up-Regulation, Viral Matrix Proteins genetics, Gene Expression Regulation, Neoplastic, Herpesvirus 4, Human metabolism, Hodgkin Disease metabolism, Nuclear Proteins metabolism, Proto-Oncogene Proteins metabolism, Repressor Proteins metabolism, Viral Matrix Proteins metabolism
- Abstract
Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-kappaB signaling. We also show that Bmi-1 is up-regulated by NF-kappaB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-kappaB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
- Published
- 2007
- Full Text
- View/download PDF